var bibbase_data = {"data":"<img src=\"//bibbase.org/img/ajax-loader.gif\" id=\"spinner\"\n  style=\"display: none;\" alt=\"Loading..\" />\n\n<div id=\"bibbase\">\n\n  <script type=\"text/javascript\">\n    var bibbase = {\n      params: {\"bib\":\"https://bibbase.org/zotero-mypublications/arbones\",\"jsonp\":\"1\",\"host\":\"bibbase.org\",\"ssl\":false},\n      data: [{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"CRISPR/Cas9-mediated deletion of adipocyte genes associated with NAFLD alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro\",\"volume\":\"325\",\"copyright\":\"All rights reserved\",\"issn\":\"0363-6143, 1522-1563\",\"url\":\"https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023\",\"doi\":\"10.1152/ajpcell.00291.2023\",\"abstract\":\"Obesity is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD), and the subcutaneous white adipose tissue (scWAT) is the primary lipid storage depot and regulates lipid fluxes to other organs. Our previous work identified genes upregulated in scWAT of patients with NAFLD: SOCS3, DUSP1, and SIK1. Herein, we knocked down (KD) their expression in human adipose-derived mesenchymal stem cells (hADMSCs) using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology and characterized their phenotype. We found that SOCS3, DUSP1, and SIK1 expression in hADMSC-derived adipocytes was not critical for adipogenesis. However, the metabolic characterization of the cells suggested that the genes played important roles in lipid metabolism. Reduction of SIK1 expression significantly increased both de novo lipogenesis (DNL) and palmitate-induced lipogenesis (PIL). Editing out SOCS3 reduced DNL while increasing isoproterenolinduced lipolysis and insulin-induced palmitate accumulation. Conversely, DUSP1 reduced PIL and DNL. Moreover, RNAsequencing analysis of edited cells showed that these genes not only altered lipid metabolism but also other biological pathways related to inflammatory processes, in the case of DUSP1, extracellular matrix remodeling for SOCS3, or cellular transport for SIK1. Finally, to evaluate a possible adipocyte-hepatocyte axis, human hepatoma HepG2 cells were cocultured with edited hADMSCs-derived adipocytes in the presence of [3H]-palmitate. All HepG2 cells cultured with DUSP1-, SIK1-, or SOCS3-KD adipocytes decreased [3H]-palmitate accumulation compared with control adipocytes. These results support our hypotheses that SOCS3, DUSP1, and SIK1 regulate multiple aspects of adipocyte function, which may play a role in the progression of obesityassociated comorbidities, such as NAFLD.\",\"language\":\"en\",\"number\":\"5\",\"urldate\":\"2023-10-31\",\"journal\":\"American Journal of Physiology-Cell Physiology\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Lopez-Yus\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Frendo-Cumbo\"],\"firstnames\":[\"Scott\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Del\",\"Moral-Bergos\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rydén\"],\"firstnames\":[\"Mikael\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lorente-Cebrian\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"November\",\"year\":\"2023\",\"pages\":\"C1178–C1189\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view\",\"bibtex\":\"@article{lopez-yus_crispr/cas9-mediated_2023,\\n\\ttitle = {{CRISPR}/{Cas9}-mediated deletion of adipocyte genes associated with {NAFLD} alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro},\\n\\tvolume = {325},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {0363-6143, 1522-1563},\\n\\turl = {https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023},\\n\\tdoi = {10.1152/ajpcell.00291.2023},\\n\\tabstract = {Obesity is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD), and the subcutaneous white adipose tissue (scWAT) is the primary lipid storage depot and regulates lipid fluxes to other organs. Our previous work identified genes upregulated in scWAT of patients with NAFLD: SOCS3, DUSP1, and SIK1. Herein, we knocked down (KD) their expression in human adipose-derived mesenchymal stem cells (hADMSCs) using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology and characterized their phenotype. We found that SOCS3, DUSP1, and SIK1 expression in hADMSC-derived adipocytes was not critical for adipogenesis. However, the metabolic characterization of the cells suggested that the genes played important roles in lipid metabolism. Reduction of SIK1 expression significantly increased both de novo lipogenesis (DNL) and palmitate-induced lipogenesis (PIL). Editing out SOCS3 reduced DNL while increasing isoproterenolinduced lipolysis and insulin-induced palmitate accumulation. Conversely, DUSP1 reduced PIL and DNL. Moreover, RNAsequencing analysis of edited cells showed that these genes not only altered lipid metabolism but also other biological pathways related to inflammatory processes, in the case of DUSP1, extracellular matrix remodeling for SOCS3, or cellular transport for SIK1. Finally, to evaluate a possible adipocyte-hepatocyte axis, human hepatoma HepG2 cells were cocultured with edited hADMSCs-derived adipocytes in the presence of [3H]-palmitate. All HepG2 cells cultured with DUSP1-, SIK1-, or SOCS3-KD adipocytes decreased [3H]-palmitate accumulation compared with control adipocytes. These results support our hypotheses that SOCS3, DUSP1, and SIK1 regulate multiple aspects of adipocyte function, which may play a role in the progression of obesityassociated comorbidities, such as NAFLD.},\\n\\tlanguage = {en},\\n\\tnumber = {5},\\n\\turldate = {2023-10-31},\\n\\tjournal = {American Journal of Physiology-Cell Physiology},\\n\\tauthor = {Lopez-Yus, Marta and Frendo-Cumbo, Scott and Del Moral-Bergos, Raquel and Garcia-Sobreviela, Maria Pilar and Bernal-Monterde, Vanesa and Rydén, Mikael and Lorente-Cebrian, Silvia and Arbones-Mainar, Jose M.},\\n\\tmonth = nov,\\n\\tyear = {2023},\\n\\tpages = {C1178--C1189},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Lopez-Yus, M.\",\"Frendo-Cumbo, S.\",\"Del Moral-Bergos, R.\",\"Garcia-Sobreviela, M. P.\",\"Bernal-Monterde, V.\",\"Rydén, M.\",\"Lorente-Cebrian, S.\",\"Arbones-Mainar, J. M.\"],\"key\":\"lopez-yus_crispr/cas9-mediated_2023\",\"id\":\"lopez-yus_crispr/cas9-mediated_2023\",\"bibbaseid\":\"lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications\",\"volume\":\"24\",\"copyright\":\"All rights reserved\",\"doi\":\"10.3390/ijms24087468\",\"abstract\":\"Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.\",\"number\":\"8\",\"journal\":\"International Journal of Molecular Sciences\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Lopez-Yus\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"García-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[\"del\"],\"lastnames\":[\"Moral-Bergos\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"April\",\"year\":\"2023\",\"note\":\"Publisher: MDPI\",\"bibtex\":\"@article{lopez-yus_gene_2023,\\n\\ttitle = {Gene {Therapy} {Based} on {Mesenchymal} {Stem} {Cells} {Derived} from {Adipose} {Tissue} for the {Treatment} of {Obesity} and {Its} {Metabolic} {Complications}},\\n\\tvolume = {24},\\n\\tcopyright = {All rights reserved},\\n\\tdoi = {10.3390/ijms24087468},\\n\\tabstract = {Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.},\\n\\tnumber = {8},\\n\\tjournal = {International Journal of Molecular Sciences},\\n\\tauthor = {Lopez-Yus, Marta and García-Sobreviela, Maria Pilar and del Moral-Bergos, Raquel and Arbones-Mainar, Jose M.},\\n\\tmonth = apr,\\n\\tyear = {2023},\\n\\tnote = {Publisher: MDPI},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Lopez-Yus, M.\",\"García-Sobreviela, M. P.\",\"del Moral-Bergos, R.\",\"Arbones-Mainar, J. M.\"],\"key\":\"lopez-yus_gene_2023\",\"id\":\"lopez-yus_gene_2023\",\"bibbaseid\":\"lopezyus-garcasobreviela-delmoralbergos-arbonesmainar-genetherapybasedonmesenchymalstemcellsderivedfromadiposetissueforthetreatmentofobesityanditsmetaboliccomplications-2023\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression\",\"volume\":\"36\",\"copyright\":\"All rights reserved\",\"doi\":\"10.1096/fj.202200118RR\",\"abstract\":\"Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.\",\"number\":\"8\",\"journal\":\"FASEB Journal\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Lopez-Yus\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lorente-Cebrian\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[\"del\"],\"lastnames\":[\"Moral-Bergos\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hörndler\"],\"firstnames\":[\"Carlos\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Casamayor\"],\"firstnames\":[\"Carmen\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"August\",\"year\":\"2022\",\"note\":\"Publisher: John Wiley and Sons Inc\",\"bibtex\":\"@article{lopez-yus_identification_2022,\\n\\ttitle = {Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression},\\n\\tvolume = {36},\\n\\tcopyright = {All rights reserved},\\n\\tdoi = {10.1096/fj.202200118RR},\\n\\tabstract = {Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.},\\n\\tnumber = {8},\\n\\tjournal = {FASEB Journal},\\n\\tauthor = {Lopez-Yus, Marta and Lorente-Cebrian, Silvia and del Moral-Bergos, Raquel and Hörndler, Carlos and Garcia-Sobreviela, Maria Pilar and Casamayor, Carmen and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},\\n\\tmonth = aug,\\n\\tyear = {2022},\\n\\tnote = {Publisher: John Wiley and Sons Inc},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Lopez-Yus, M.\",\"Lorente-Cebrian, S.\",\"del Moral-Bergos, R.\",\"Hörndler, C.\",\"Garcia-Sobreviela, M. P.\",\"Casamayor, C.\",\"Sanz-Paris, A.\",\"Bernal-Monterde, V.\",\"Arbones-Mainar, J. M.\"],\"key\":\"lopez-yus_identification_2022\",\"id\":\"lopez-yus_identification_2022\",\"bibbaseid\":\"lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice\",\"volume\":\"74\",\"copyright\":\"All rights reserved\",\"issn\":\"2212-8778\",\"url\":\"https://www.sciencedirect.com/science/article/pii/S2212877823000832\",\"doi\":\"10.1016/j.molmet.2023.101749\",\"abstract\":\"Objective Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. Methods MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice. Results In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice. Conclusions These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.\",\"language\":\"en\",\"urldate\":\"2023-06-22\",\"journal\":\"Molecular Metabolism\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Laiglesia\"],\"firstnames\":[\"Laura\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Escoté\"],\"firstnames\":[\"Xavier\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sáinz\"],\"firstnames\":[\"Neira\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Felix-Soriano\"],\"firstnames\":[\"Elisa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Santamaría\"],\"firstnames\":[\"Eva\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Collantes\"],\"firstnames\":[\"María\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Fernández-Galilea\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Colón-Mesa\"],\"firstnames\":[\"Ignacio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez-Fernández\"],\"firstnames\":[\"Leyre\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Quesada-López\"],\"firstnames\":[\"Tania\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Quesada-Vázquez\"],\"firstnames\":[\"Sergio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rodríguez-Ortigosa\"],\"firstnames\":[\"Carlos\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"José\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Valverde\"],\"firstnames\":[\"Ángela\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez\"],\"firstnames\":[\"J\",\"Alfredo\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Dalli\"],\"firstnames\":[\"Jesmond\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Herrero\"],\"firstnames\":[\"Laura\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lorente-Cebrián\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Villarroya\"],\"firstnames\":[\"Francesc\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moreno-Aliaga\"],\"firstnames\":[\"María\",\"J.\"],\"suffixes\":[]}],\"month\":\"August\",\"year\":\"2023\",\"pages\":\"101749\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view\",\"bibtex\":\"@article{laiglesia_maresin_2023,\\n\\ttitle = {Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice},\\n\\tvolume = {74},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {2212-8778},\\n\\turl = {https://www.sciencedirect.com/science/article/pii/S2212877823000832},\\n\\tdoi = {10.1016/j.molmet.2023.101749},\\n\\tabstract = {Objective\\nMaresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning.\\nMethods\\nMaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice.\\nResults\\nIn cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice.\\nConclusions\\nThese data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.},\\n\\tlanguage = {en},\\n\\turldate = {2023-06-22},\\n\\tjournal = {Molecular Metabolism},\\n\\tauthor = {Laiglesia, Laura M. and Escoté, Xavier and Sáinz, Neira and Felix-Soriano, Elisa and Santamaría, Eva and Collantes, María and Fernández-Galilea, Marta and Colón-Mesa, Ignacio and Martínez-Fernández, Leyre and Quesada-López, Tania and Quesada-Vázquez, Sergio and Rodríguez-Ortigosa, Carlos and Arbones-Mainar, José M. and Valverde, Ángela M. and Martínez, J Alfredo and Dalli, Jesmond and Herrero, Laura and Lorente-Cebrián, Silvia and Villarroya, Francesc and Moreno-Aliaga, María J.},\\n\\tmonth = aug,\\n\\tyear = {2023},\\n\\tpages = {101749},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view}\\n}\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Laiglesia, L. M.\",\"Escoté, X.\",\"Sáinz, N.\",\"Felix-Soriano, E.\",\"Santamaría, E.\",\"Collantes, M.\",\"Fernández-Galilea, M.\",\"Colón-Mesa, I.\",\"Martínez-Fernández, L.\",\"Quesada-López, T.\",\"Quesada-Vázquez, S.\",\"Rodríguez-Ortigosa, C.\",\"Arbones-Mainar, J. M.\",\"Valverde, Á. M.\",\"Martínez, J A.\",\"Dalli, J.\",\"Herrero, L.\",\"Lorente-Cebrián, S.\",\"Villarroya, F.\",\"Moreno-Aliaga, M. J.\"],\"key\":\"laiglesia_maresin_2023\",\"id\":\"laiglesia_maresin_2023\",\"bibbaseid\":\"laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.sciencedirect.com/science/article/pii/S2212877823000832\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals\",\"volume\":\"375\",\"copyright\":\"All rights reserved\",\"issn\":\"00219150\",\"url\":\"https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867\",\"doi\":\"10.1016/j.atherosclerosis.2023.05.003\",\"abstract\":\"Background & aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardio­ vascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradi­ cation of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy. Methods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR). Results: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (− 22%) and HDL-TG (− 18%) after one-year follow-up. Conclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this asso­ ciation. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evo­ lution of glucose tolerance and IR after HCV eradication.\",\"language\":\"en\",\"urldate\":\"2023-05-31\",\"journal\":\"Atherosclerosis\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Casas-Deza\"],\"firstnames\":[\"Diego\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Espina\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez-Sapiña\"],\"firstnames\":[\"Ana\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Del\",\"Moral-Bergos\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lopez-Yus\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Calmarza\"],\"firstnames\":[\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"June\",\"year\":\"2023\",\"pages\":\"59–66\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view\",\"bibtex\":\"@article{casas-deza_triglyceride-rich_2023,\\n\\ttitle = {Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis {C} receiving direct-acting antivirals},\\n\\tvolume = {375},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {00219150},\\n\\turl = {https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867},\\n\\tdoi = {10.1016/j.atherosclerosis.2023.05.003},\\n\\tabstract = {Background \\\\& aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardio­ vascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradi­ cation of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy.\\nMethods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR).\\nResults: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (− 22\\\\%) and HDL-TG (− 18\\\\%) after one-year follow-up.\\nConclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this asso­ ciation. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evo­ lution of glucose tolerance and IR after HCV eradication.},\\n\\tlanguage = {en},\\n\\turldate = {2023-05-31},\\n\\tjournal = {Atherosclerosis},\\n\\tauthor = {Casas-Deza, Diego and Espina, Silvia and Martínez-Sapiña, Ana and Del Moral-Bergos, Raquel and Garcia-Sobreviela, Maria Pilar and Lopez-Yus, Marta and Calmarza, Pilar and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},\\n\\tmonth = jun,\\n\\tyear = {2023},\\n\\tpages = {59--66},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view}\\n}\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Casas-Deza, D.\",\"Espina, S.\",\"Martínez-Sapiña, A.\",\"Del Moral-Bergos, R.\",\"Garcia-Sobreviela, M. P.\",\"Lopez-Yus, M.\",\"Calmarza, P.\",\"Bernal-Monterde, V.\",\"Arbones-Mainar, J. M.\"],\"key\":\"casas-deza_triglyceride-rich_2023\",\"id\":\"casas-deza_triglyceride-rich_2023\",\"bibbaseid\":\"casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease\",\"volume\":\"11\",\"copyright\":\"http://creativecommons.org/licenses/by/3.0/\",\"issn\":\"2077-0383\",\"url\":\"https://www.mdpi.com/2077-0383/11/14/4049\",\"doi\":\"10.3390/jcm11144049\",\"abstract\":\"Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.\",\"language\":\"en\",\"number\":\"14\",\"urldate\":\"2022-12-15\",\"journal\":\"Journal of Clinical Medicine\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Casas-Deza\"],\"firstnames\":[\"Diego\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez-Sapiña\"],\"firstnames\":[\"Ana\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Espina\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Rodriguez\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Fernandez-Bonilla\"],\"firstnames\":[\"Eva\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gonzalez-Irazabal\"],\"firstnames\":[\"Yolanda\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"January\",\"year\":\"2022\",\"note\":\"Number: 14 Publisher: Multidisciplinary Digital Publishing Institute\",\"pages\":\"4049\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view\",\"bibtex\":\"@article{casas-deza_evaluation_2022,\\n\\ttitle = {Evaluation of {Cardiovascular} {Risk} {Factors} after {Hepatitis} {C} {Virus} {Eradication} with {Direct}-{Acting} {Antivirals} in a {Cohort} of {Treatment}-{Naïve} {Patients} without {History} of {Cardiovascular} {Disease}},\\n\\tvolume = {11},\\n\\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\\n\\tissn = {2077-0383},\\n\\turl = {https://www.mdpi.com/2077-0383/11/14/4049},\\n\\tdoi = {10.3390/jcm11144049},\\n\\tabstract = {Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53\\\\% female, 9.6\\\\% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4\\\\% of patients, requiring initiation of statins in 15\\\\%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.},\\n\\tlanguage = {en},\\n\\tnumber = {14},\\n\\turldate = {2022-12-15},\\n\\tjournal = {Journal of Clinical Medicine},\\n\\tauthor = {Casas-Deza, Diego and Martínez-Sapiña, Ana and Espina, Silvia and Garcia-Rodriguez, Beatriz and Fernandez-Bonilla, Eva M. and Sanz-Paris, Alejandro and Gonzalez-Irazabal, Yolanda and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},\\n\\tmonth = jan,\\n\\tyear = {2022},\\n\\tnote = {Number: 14\\nPublisher: Multidisciplinary Digital Publishing Institute},\\n\\tpages = {4049},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view}\\n}\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Casas-Deza, D.\",\"Martínez-Sapiña, A.\",\"Espina, S.\",\"Garcia-Rodriguez, B.\",\"Fernandez-Bonilla, E. M.\",\"Sanz-Paris, A.\",\"Gonzalez-Irazabal, Y.\",\"Bernal-Monterde, V.\",\"Arbones-Mainar, J. M.\"],\"key\":\"casas-deza_evaluation_2022\",\"id\":\"casas-deza_evaluation_2022\",\"bibbaseid\":\"casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.mdpi.com/2077-0383/11/14/4049\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Role of Branched-Chain Amino Acids and Their Derivative β-Hydroxy-β-Methylbutyrate in Liver Cirrhosis\",\"volume\":\"11\",\"copyright\":\"http://creativecommons.org/licenses/by/3.0/\",\"issn\":\"2077-0383\",\"url\":\"https://www.mdpi.com/2077-0383/11/24/7337\",\"doi\":\"10.3390/jcm11247337\",\"abstract\":\"Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.\",\"language\":\"en\",\"number\":\"24\",\"urldate\":\"2022-12-13\",\"journal\":\"Journal of Clinical Medicine\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Espina\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Casas-Deza\"],\"firstnames\":[\"Diego\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbonés-Mainar\"],\"firstnames\":[\"Jose\",\"Miguel\"],\"suffixes\":[]}],\"month\":\"January\",\"year\":\"2022\",\"note\":\"Number: 24 Publisher: Multidisciplinary Digital Publishing Institute\",\"pages\":\"7337\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view\",\"bibtex\":\"@article{espina_role_2022,\\n\\ttitle = {Role of {Branched}-{Chain} {Amino} {Acids} and {Their} {Derivative} β-{Hydroxy}-β-{Methylbutyrate} in {Liver} {Cirrhosis}},\\n\\tvolume = {11},\\n\\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\\n\\tissn = {2077-0383},\\n\\turl = {https://www.mdpi.com/2077-0383/11/24/7337},\\n\\tdoi = {10.3390/jcm11247337},\\n\\tabstract = {Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.},\\n\\tlanguage = {en},\\n\\tnumber = {24},\\n\\turldate = {2022-12-13},\\n\\tjournal = {Journal of Clinical Medicine},\\n\\tauthor = {Espina, Silvia and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Casas-Deza, Diego and Arbonés-Mainar, Jose Miguel},\\n\\tmonth = jan,\\n\\tyear = {2022},\\n\\tnote = {Number: 24\\nPublisher: Multidisciplinary Digital Publishing Institute},\\n\\tpages = {7337},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view}\\n}\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Espina, S.\",\"Sanz-Paris, A.\",\"Bernal-Monterde, V.\",\"Casas-Deza, D.\",\"Arbonés-Mainar, J. M.\"],\"key\":\"espina_role_2022\",\"id\":\"espina_role_2022\",\"bibbaseid\":\"espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.mdpi.com/2077-0383/11/24/7337\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn’s Disease: Real World Evidence From the ENEIDA Registry\",\"copyright\":\"All rights reserved\",\"issn\":\"1873-9946, 1876-4479\",\"shorttitle\":\"Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn’s Disease\",\"url\":\"https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892\",\"doi\":\"10.1093/ecco-jcc/jjac108\",\"abstract\":\"Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods: Elderly patients [\\\\textgreater60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. Results: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Conclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.\",\"language\":\"en\",\"urldate\":\"2022-09-29\",\"journal\":\"Journal of Crohn's and Colitis\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Casas-Deza\"],\"firstnames\":[\"Diego\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lamuela-Calvo\"],\"firstnames\":[\"Luis\",\"Javier\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gomollón\"],\"firstnames\":[\"Fernando\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbonés-Mainar\"],\"firstnames\":[\"José\",\"Miguel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Caballol\"],\"firstnames\":[\"Berta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gisbert\"],\"firstnames\":[\"Javier\",\"P\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rivero\"],\"firstnames\":[\"Montserrat\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sánchez-Rodríguez\"],\"firstnames\":[\"Eugenia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arias\",\"García\"],\"firstnames\":[\"Lara\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gutiérrez\",\"Casbas\"],\"firstnames\":[\"Ana\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Merino\"],\"firstnames\":[\"Olga\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Márquez\"],\"firstnames\":[\"Lucía\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Laredo\"],\"firstnames\":[\"Viviana\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martín-Arranz\"],\"firstnames\":[\"María\",\"Dolores\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"López\",\"Serrano\"],\"firstnames\":[\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Riestra\",\"Menéndez\"],\"firstnames\":[\"Sabino\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"González-Muñoza\"],\"firstnames\":[\"Carlos\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Castro\",\"Parga\"],\"firstnames\":[\"Luisa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Calvo\",\"Moya\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Fuentes-Valenzuela\"],\"firstnames\":[\"Esteban\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Esteve\"],\"firstnames\":[\"Maria\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Iborra\"],\"firstnames\":[\"Marisa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Dura\",\"Gil\"],\"firstnames\":[\"Miguel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Barreiro-De\",\"Acosta\"],\"firstnames\":[\"Manuel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lorente-Poyatos\"],\"firstnames\":[\"Rufo\",\"Humberto\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Manceñido\"],\"firstnames\":[\"Noemí\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Calafat\"],\"firstnames\":[\"Margalida\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rodríguez-Lago\"],\"firstnames\":[\"Iago\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Guardiola\",\"Capo\"],\"firstnames\":[\"Jordi\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Payeras\"],\"firstnames\":[\"Maria\",\"Antonia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Morales\",\"Alvarado\"],\"firstnames\":[\"Víctor\",\"Jair\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Tardillo\"],\"firstnames\":[\"Carlos\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bujanda\"],\"firstnames\":[\"Luis\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Muñoz-Nuñez\"],\"firstnames\":[\"José\",\"Fernando\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ber\",\"Nieto\"],\"firstnames\":[\"Yolanda\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bermejo\"],\"firstnames\":[\"Fernando\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Almela\"],\"firstnames\":[\"Pedro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro-Llavat\"],\"firstnames\":[\"Mercè\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez\",\"Montiel\"],\"firstnames\":[\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rodríguez\",\"Gutiérrez\"],\"firstnames\":[\"Cristina\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Van\",\"Domselaar\"],\"firstnames\":[\"Manuel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sesé\"],\"firstnames\":[\"Eva\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez\",\"Pérez\"],\"firstnames\":[\"Teresa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ricart\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Chaparro\"],\"firstnames\":[\"María\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"García\"],\"firstnames\":[\"María\",\"José\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"López-Sanromán\"],\"firstnames\":[\"Antonio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sicilia\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Orts\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"López-García\"],\"firstnames\":[\"Alicia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martín-Arranz\"],\"firstnames\":[\"Eduardo\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pérez-Calle\"],\"firstnames\":[\"José\",\"Lázaro\"],\"suffixes\":[]},{\"propositions\":[\"de\"],\"lastnames\":[\"Francisco\"],\"firstnames\":[\"Ruth\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"García-Planella\"],\"firstnames\":[\"Esther\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Domènech\"],\"firstnames\":[\"Eugeni\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"García-López\"],\"firstnames\":[\"y\",\"Santiago\"],\"suffixes\":[]}],\"month\":\"August\",\"year\":\"2022\",\"pages\":\"jjac108\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view\",\"bibtex\":\"@article{casas-deza_effectiveness_2022,\\n\\ttitle = {Effectiveness and {Safety} of {Ustekinumab} in {Elderly} {Patients} with {Crohn}’s {Disease}: {Real} {World} {Evidence} {From} the {ENEIDA} {Registry}},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1873-9946, 1876-4479},\\n\\tshorttitle = {Effectiveness and {Safety} of {Ustekinumab} in {Elderly} {Patients} with {Crohn}’s {Disease}},\\n\\turl = {https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892},\\n\\tdoi = {10.1093/ecco-jcc/jjac108},\\n\\tabstract = {Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD.\\nMethods: Elderly patients [{\\\\textgreater}60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54.\\nResults: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4\\\\%, p = 0.20], 32 [53.0\\\\% vs 54.5\\\\%, p = 0.26] and 54 [57.8\\\\% vs 51.1\\\\%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2\\\\% vs 11.2\\\\%, p = 0.350], including severe infections [7.1\\\\% vs 7.3\\\\%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7\\\\% vs 4.3\\\\%, p = 0.003].\\nConclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.},\\n\\tlanguage = {en},\\n\\turldate = {2022-09-29},\\n\\tjournal = {Journal of Crohn's and Colitis},\\n\\tauthor = {Casas-Deza, Diego and Lamuela-Calvo, Luis Javier and Gomollón, Fernando and Arbonés-Mainar, José Miguel and Caballol, Berta and Gisbert, Javier P and Rivero, Montserrat and Sánchez-Rodríguez, Eugenia and Arias García, Lara and Gutiérrez Casbas, Ana and Merino, Olga and Márquez, Lucía and Laredo, Viviana and Martín-Arranz, María Dolores and López Serrano, Pilar and Riestra Menéndez, Sabino and González-Muñoza, Carlos and de Castro Parga, Luisa and Calvo Moya, Marta and Fuentes-Valenzuela, Esteban and Esteve, Maria and Iborra, Marisa and Dura Gil, Miguel and Barreiro-De Acosta, Manuel and Lorente-Poyatos, Rufo Humberto and Manceñido, Noemí and Calafat, Margalida and Rodríguez-Lago, Iago and Guardiola Capo, Jordi and Payeras, Maria Antonia and Morales Alvarado, Víctor Jair and Tardillo, Carlos and Bujanda, Luis and Muñoz-Nuñez, José Fernando and Ber Nieto, Yolanda and Bermejo, Fernando and Almela, Pedro and Navarro-Llavat, Mercè and Martínez Montiel, Pilar and Rodríguez Gutiérrez, Cristina and Van Domselaar, Manuel and Sesé, Eva and Martínez Pérez, Teresa and Ricart, Elena and Chaparro, María and García, María José and López-Sanromán, Antonio and Sicilia, Beatriz and Orts, Beatriz and López-García, Alicia and Martín-Arranz, Eduardo and Pérez-Calle, José Lázaro and de Francisco, Ruth and García-Planella, Esther and Domènech, Eugeni and García-López, y Santiago},\\n\\tmonth = aug,\\n\\tyear = {2022},\\n\\tpages = {jjac108},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Casas-Deza, D.\",\"Lamuela-Calvo, L. J.\",\"Gomollón, F.\",\"Arbonés-Mainar, J. M.\",\"Caballol, B.\",\"Gisbert, J. P\",\"Rivero, M.\",\"Sánchez-Rodríguez, E.\",\"Arias García, L.\",\"Gutiérrez Casbas, A.\",\"Merino, O.\",\"Márquez, L.\",\"Laredo, V.\",\"Martín-Arranz, M. D.\",\"López Serrano, P.\",\"Riestra Menéndez, S.\",\"González-Muñoza, C.\",\"de Castro Parga, L.\",\"Calvo Moya, M.\",\"Fuentes-Valenzuela, E.\",\"Esteve, M.\",\"Iborra, M.\",\"Dura Gil, M.\",\"Barreiro-De Acosta, M.\",\"Lorente-Poyatos, R. H.\",\"Manceñido, N.\",\"Calafat, M.\",\"Rodríguez-Lago, I.\",\"Guardiola Capo, J.\",\"Payeras, M. A.\",\"Morales Alvarado, V. J.\",\"Tardillo, C.\",\"Bujanda, L.\",\"Muñoz-Nuñez, J. F.\",\"Ber Nieto, Y.\",\"Bermejo, F.\",\"Almela, P.\",\"Navarro-Llavat, M.\",\"Martínez Montiel, P.\",\"Rodríguez Gutiérrez, C.\",\"Van Domselaar, M.\",\"Sesé, E.\",\"Martínez Pérez, T.\",\"Ricart, E.\",\"Chaparro, M.\",\"García, M. J.\",\"López-Sanromán, A.\",\"Sicilia, B.\",\"Orts, B.\",\"López-García, A.\",\"Martín-Arranz, E.\",\"Pérez-Calle, J. L.\",\"de Francisco, R.\",\"García-Planella, E.\",\"Domènech, E.\",\"García-López, y S.\"],\"key\":\"casas-deza_effectiveness_2022\",\"id\":\"casas-deza_effectiveness_2022\",\"bibbaseid\":\"casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"downloads\":1,\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Apolipoprotein E knock-out and knock-in mice: Atherosclerosis, metabolic syndrome, and beyond\",\"volume\":\"50\",\"copyright\":\"All rights reserved\",\"issn\":\"00222275\",\"doi\":\"10.1194/jlr.R800070-JLR200\",\"abstract\":\"Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to studymultiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases. Copyright ©2009 by the American Society for Biochemistry and Molecular Biology, Inc.\",\"number\":\"SUPPL.\",\"journal\":\"Journal of Lipid Research\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Pendse\"],\"firstnames\":[\"A.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"L.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Altenburg\"],\"firstnames\":[\"M.K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"N.\"],\"suffixes\":[]}],\"year\":\"2009\",\"bibtex\":\"@article{pendse_apolipoprotein_2009,\\n\\ttitle = {Apolipoprotein {E} knock-out and knock-in mice: {Atherosclerosis}, metabolic syndrome, and beyond},\\n\\tvolume = {50},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {00222275},\\n\\tdoi = {10.1194/jlr.R800070-JLR200},\\n\\tabstract = {Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to studymultiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases. Copyright ©2009 by the American Society for Biochemistry and Molecular Biology, Inc.},\\n\\tnumber = {SUPPL.},\\n\\tjournal = {Journal of Lipid Research},\\n\\tauthor = {Pendse, A.A. and Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Maeda, N.},\\n\\tyear = {2009},\\n}\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Pendse, A.\",\"Arbones-Mainar, J.\",\"Johnson, L.\",\"Altenburg, M.\",\"Maeda, N.\"],\"key\":\"pendse_apolipoprotein_2009\",\"id\":\"pendse_apolipoprotein_2009\",\"bibbaseid\":\"pendse-arbonesmainar-johnson-altenburg-maeda-apolipoproteineknockoutandknockinmiceatherosclerosismetabolicsyndromeandbeyond-2009\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression\",\"volume\":\"36\",\"copyright\":\"All rights reserved\",\"issn\":\"0892-6638\",\"url\":\"https://doi.org/10.1096/fj.202200118RR\",\"doi\":\"https://doi.org/10.1096/fj.202200118RR\",\"abstract\":\"Abstract Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.\",\"number\":\"8\",\"journal\":\"The FASEB Journal\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Lopez-Yus\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lorente-Cebrian\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[\"del\"],\"lastnames\":[\"Moral-Bergos\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hörndler\"],\"firstnames\":[\"Carlos\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Casamayor\"],\"firstnames\":[\"Carmen\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M\"],\"suffixes\":[]}],\"month\":\"August\",\"year\":\"2022\",\"note\":\"Publisher: John Wiley & Sons, Ltd\",\"pages\":\"e22429\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view\",\"bibtex\":\"@article{lopez-yus_identification_2022,\\n\\ttitle = {Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression},\\n\\tvolume = {36},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {0892-6638},\\n\\turl = {https://doi.org/10.1096/fj.202200118RR},\\n\\tdoi = {https://doi.org/10.1096/fj.202200118RR},\\n\\tabstract = {Abstract Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.},\\n\\tnumber = {8},\\n\\tjournal = {The FASEB Journal},\\n\\tauthor = {Lopez-Yus, Marta and Lorente-Cebrian, Silvia and del Moral-Bergos, Raquel and Hörndler, Carlos and Garcia-Sobreviela, Maria Pilar and Casamayor, Carmen and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M},\\n\\tmonth = aug,\\n\\tyear = {2022},\\n\\tnote = {Publisher: John Wiley \\\\& Sons, Ltd},\\n\\tpages = {e22429},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view}\\n}\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Lopez-Yus, M.\",\"Lorente-Cebrian, S.\",\"del Moral-Bergos, R.\",\"Hörndler, C.\",\"Garcia-Sobreviela, M. P.\",\"Casamayor, C.\",\"Sanz-Paris, A.\",\"Bernal-Monterde, V.\",\"Arbones-Mainar, J. M\"],\"key\":\"lopez-yus_identification_2022-1\",\"id\":\"lopez-yus_identification_2022-1\",\"bibbaseid\":\"lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://doi.org/10.1096/fj.202200118RR\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition\",\"copyright\":\"All rights reserved\",\"issn\":\"18778755\",\"url\":\"https://doi.org/10.1007/s13105-021-00836-7\",\"doi\":\"10.1007/s13105-021-00836-7\",\"abstract\":\"Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.\",\"number\":\"0123456789\",\"journal\":\"Journal of Physiology and Biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Lopez-Yus\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lopez-Perez\"],\"firstnames\":[\"Rebeca\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[\"del\"],\"lastnames\":[\"Moral-Bergos\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lorente-Cebrian\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"year\":\"2021\",\"note\":\"Publisher: Springer Netherlands ISBN: 0123456789\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view\",\"bibtex\":\"@article{lopez-yus_adiponectin_2021,\\n\\ttitle = {Adiponectin overexpression in {C2C12} myocytes increases lipid oxidation and myofiber transition},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {18778755},\\n\\turl = {https://doi.org/10.1007/s13105-021-00836-7},\\n\\tdoi = {10.1007/s13105-021-00836-7},\\n\\tabstract = {Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.},\\n\\tnumber = {0123456789},\\n\\tjournal = {Journal of Physiology and Biochemistry},\\n\\tauthor = {Lopez-Yus, Marta and Lopez-Perez, Rebeca and Garcia-Sobreviela, Maria Pilar and del Moral-Bergos, Raquel and Lorente-Cebrian, Silvia and Arbones-Mainar, Jose M.},\\n\\tyear = {2021},\\n\\tnote = {Publisher: Springer Netherlands\\nISBN: 0123456789},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Lopez-Yus, M.\",\"Lopez-Perez, R.\",\"Garcia-Sobreviela, M. P.\",\"del Moral-Bergos, R.\",\"Lorente-Cebrian, S.\",\"Arbones-Mainar, J. M.\"],\"key\":\"lopez-yus_adiponectin_2021\",\"id\":\"lopez-yus_adiponectin_2021\",\"bibbaseid\":\"lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://doi.org/10.1007/s13105-021-00836-7\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes\",\"volume\":\"19\",\"copyright\":\"All rights reserved\",\"issn\":\"1422-0067\",\"url\":\"http://www.mdpi.com/1422-0067/19/7/2081\",\"doi\":\"10.3390/ijms19072081\",\"abstract\":\"Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty μM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.\",\"number\":\"7\",\"journal\":\"International Journal of Molecular Sciences\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Carpéné\"],\"firstnames\":[\"Christian\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pejenaute\"],\"firstnames\":[\"Héctor\"],\"suffixes\":[]},{\"propositions\":[\"del\"],\"lastnames\":[\"Moral\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Boulet\"],\"firstnames\":[\"Nathalie\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hijona\"],\"firstnames\":[\"Elizabeth\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Andrade\"],\"firstnames\":[\"Fernando\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Villanueva-Millán\"],\"firstnames\":[\"J\",\"Maria\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aguirre\"],\"firstnames\":[\"Leixuri\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"José\",\"Miguel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Villanueva-Millán\"],\"firstnames\":[\"Maria\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aguirre\"],\"firstnames\":[\"Leixuri\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"José\",\"Miguel\"],\"suffixes\":[]}],\"year\":\"2018\",\"note\":\"ISBN: 1422-0067\",\"pages\":\"2081\",\"bibtex\":\"@article{Carpene2018,\\n\\ttitle = {The {Dietary} {Antioxidant} {Piceatannol} {Inhibits} {Adipogenesis} of {Human} {Adipose} {Mesenchymal} {Stem} {Cells} and {Limits} {Glucose} {Transport} and {Lipogenic} {Activities} in {Adipocytes}},\\n\\tvolume = {19},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1422-0067},\\n\\turl = {http://www.mdpi.com/1422-0067/19/7/2081},\\n\\tdoi = {10.3390/ijms19072081},\\n\\tabstract = {Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty μM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.},\\n\\tnumber = {7},\\n\\tjournal = {International Journal of Molecular Sciences},\\n\\tauthor = {Carpéné, Christian and Pejenaute, Héctor and del Moral, Raquel and Boulet, Nathalie and Hijona, Elizabeth and Andrade, Fernando and Villanueva-Millán, J Maria and Aguirre, Leixuri and Arbones-Mainar, José Miguel and Villanueva-Millán, Maria and Aguirre, Leixuri and Arbones-Mainar, José Miguel},\\n\\tyear = {2018},\\n\\tnote = {ISBN: 1422-0067},\\n\\tpages = {2081},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Carpéné, C.\",\"Pejenaute, H.\",\"del Moral, R.\",\"Boulet, N.\",\"Hijona, E.\",\"Andrade, F.\",\"Villanueva-Millán, J M.\",\"Aguirre, L.\",\"Arbones-Mainar, J. M.\",\"Villanueva-Millán, M.\",\"Aguirre, L.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Carpene2018\",\"id\":\"Carpene2018\",\"bibbaseid\":\"carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.mdpi.com/1422-0067/19/7/2081\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization\",\"volume\":\"8\",\"copyright\":\"All rights reserved\",\"url\":\"https://www.mdpi.com/2227-9059/8/9/328\",\"doi\":\"10.3390/biomedicines8090328\",\"abstract\":\"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.\",\"number\":\"9\",\"journal\":\"Biomedicines\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Bernal-Monterde\"],\"firstnames\":[\"Vanesa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Casas-Deza\"],\"firstnames\":[\"Diego\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Letona-Giménez\"],\"firstnames\":[\"Laura\"],\"suffixes\":[]},{\"propositions\":[\"de\",\"la\"],\"lastnames\":[\"Llama-Celis\"],\"firstnames\":[\"Natalia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Calmarza\"],\"firstnames\":[\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sierra-Gabarda\"],\"firstnames\":[\"Olivia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Betoré-Glaria\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez-de\",\"Lagos\"],\"firstnames\":[\"María\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez-Barredo\"],\"firstnames\":[\"Lucía\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Espinosa-Pérez\"],\"firstnames\":[\"María\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"M.\",\"Arbones-Mainar\"],\"firstnames\":[\"Jose\"],\"suffixes\":[]}],\"year\":\"2020\",\"note\":\"ISBN: 2227-9059\",\"pages\":\"328\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view\",\"bibtex\":\"@article{Bernal-Monterde2020,\\n\\ttitle = {{SARS}-{CoV}-2 {Infection} {Induces} a {Dual} {Response} in {Liver} {Function} {Tests}: {Association} with {Mortality} during {Hospitalization}},\\n\\tvolume = {8},\\n\\tcopyright = {All rights reserved},\\n\\turl = {https://www.mdpi.com/2227-9059/8/9/328},\\n\\tdoi = {10.3390/biomedicines8090328},\\n\\tabstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5\\\\%) were discharged (109 (20.5\\\\%) died). A total of 319 (64.3\\\\%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9\\\\%) and GGT (47.3\\\\%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.},\\n\\tnumber = {9},\\n\\tjournal = {Biomedicines},\\n\\tauthor = {Bernal-Monterde, Vanesa and Casas-Deza, Diego and Letona-Giménez, Laura and de la Llama-Celis, Natalia and Calmarza, Pilar and Sierra-Gabarda, Olivia and Betoré-Glaria, Elena and Martínez-de Lagos, María and Martínez-Barredo, Lucía and Espinosa-Pérez, María and M. Arbones-Mainar, Jose},\\n\\tyear = {2020},\\n\\tnote = {ISBN: 2227-9059},\\n\\tpages = {328},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Bernal-Monterde, V.\",\"Casas-Deza, D.\",\"Letona-Giménez, L.\",\"de la Llama-Celis, N.\",\"Calmarza, P.\",\"Sierra-Gabarda, O.\",\"Betoré-Glaria, E.\",\"Martínez-de Lagos, M.\",\"Martínez-Barredo, L.\",\"Espinosa-Pérez, M.\",\"M. Arbones-Mainar, J.\"],\"key\":\"Bernal-Monterde2020\",\"id\":\"Bernal-Monterde2020\",\"bibbaseid\":\"bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020\",\"role\":\"author\",\"urls\":{\"Paper\":\"https://www.mdpi.com/2227-9059/8/9/328\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Are Comorbidities Associated With Overall Survival in Patients With Oral Squamous Cell Carcinoma?\",\"volume\":\"77\",\"copyright\":\"All rights reserved\",\"issn\":\"15315053\",\"doi\":\"10.1016/j.joms.2019.03.007\",\"abstract\":\"Purpose: Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods: A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results: Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion: These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC.\",\"number\":\"9\",\"journal\":\"Journal of Oral and Maxillofacial Surgery\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Jariod-Ferrer\"],\"firstnames\":[\"Úrsula\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gavin-Clavero\"],\"firstnames\":[\"Marina\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Simón-Sanz\"],\"firstnames\":[\"M.\",\"Victoria\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moral-Saez\"],\"firstnames\":[\"Ignacio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Cisneros-Gimeno\"],\"firstnames\":[\"Ana\",\"I.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martinez-Trufero\"],\"firstnames\":[\"Javier\"],\"suffixes\":[]}],\"year\":\"2019\",\"pages\":\"1906–1914\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view\",\"bibtex\":\"@article{Jariod-Ferrer2019,\\n\\ttitle = {Are {Comorbidities} {Associated} {With} {Overall} {Survival} in {Patients} {With} {Oral} {Squamous} {Cell} {Carcinoma}?},\\n\\tvolume = {77},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {15315053},\\n\\tdoi = {10.1016/j.joms.2019.03.007},\\n\\tabstract = {Purpose: Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods: A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results: Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion: These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC.},\\n\\tnumber = {9},\\n\\tjournal = {Journal of Oral and Maxillofacial Surgery},\\n\\tauthor = {Jariod-Ferrer, Úrsula M. and Arbones-Mainar, Jose M. and Gavin-Clavero, Marina A. and Simón-Sanz, M. Victoria and Moral-Saez, Ignacio and Cisneros-Gimeno, Ana I. and Martinez-Trufero, Javier},\\n\\tyear = {2019},\\n\\tpages = {1906--1914},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Jariod-Ferrer, Ú. M.\",\"Arbones-Mainar, J. M.\",\"Gavin-Clavero, M. A.\",\"Simón-Sanz, M. V.\",\"Moral-Saez, I.\",\"Cisneros-Gimeno, A. I.\",\"Martinez-Trufero, J.\"],\"key\":\"Jariod-Ferrer2019\",\"id\":\"Jariod-Ferrer2019\",\"bibbaseid\":\"jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"GLUT12 and adipose tissue: Expression, regulation and its relation with obesity in mice\",\"copyright\":\"All rights reserved\",\"issn\":\"17481716\",\"doi\":\"10.1111/apha.13283\",\"abstract\":\"AIM The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. METHODS Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. RESULTS GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. CONCLUSION We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.\",\"number\":\"April\",\"journal\":\"Acta Physiologica\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Gil-Iturbe\"],\"firstnames\":[\"Eva\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"José\",\"Miguel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moreno-Aliaga\"],\"firstnames\":[\"María\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lostao\"],\"firstnames\":[\"María\",\"Pilar\"],\"suffixes\":[]}],\"year\":\"2019\",\"pages\":\"1–14\",\"bibtex\":\"@article{Gil-Iturbe2019,\\n\\ttitle = {{GLUT12} and adipose tissue: {Expression}, regulation and its relation with obesity in mice},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {17481716},\\n\\tdoi = {10.1111/apha.13283},\\n\\tabstract = {AIM The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. METHODS Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. RESULTS GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. CONCLUSION We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.},\\n\\tnumber = {April},\\n\\tjournal = {Acta Physiologica},\\n\\tauthor = {Gil-Iturbe, Eva and Arbones-Mainar, José Miguel and Moreno-Aliaga, María J. and Lostao, María Pilar},\\n\\tyear = {2019},\\n\\tpages = {1--14},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Gil-Iturbe, E.\",\"Arbones-Mainar, J. M.\",\"Moreno-Aliaga, M. J.\",\"Lostao, M. P.\"],\"key\":\"Gil-Iturbe2019\",\"id\":\"Gil-Iturbe2019\",\"bibbaseid\":\"giliturbe-arbonesmainar-morenoaliaga-lostao-glut12andadiposetissueexpressionregulationanditsrelationwithobesityinmice-2019\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Neck circumference is associated with nutritional status in elderly nursing home residents\",\"volume\":\"62\",\"copyright\":\"All rights reserved\",\"issn\":\"08999007\",\"doi\":\"10.1016/j.nut.2019.01.015\",\"journal\":\"Nutrition\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Serrano-Oliver\"],\"firstnames\":[\"Antonio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Torres-Anoro\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lardiés-Sanchez\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Perez-Nogueras\"],\"firstnames\":[\"Javier\"],\"suffixes\":[]}],\"year\":\"2019\",\"pages\":\"153–157\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view\",\"bibtex\":\"@article{Serrano-Oliver2019,\\n\\ttitle = {Neck circumference is associated with nutritional status in elderly nursing home residents},\\n\\tvolume = {62},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {08999007},\\n\\tdoi = {10.1016/j.nut.2019.01.015},\\n\\tjournal = {Nutrition},\\n\\tauthor = {Serrano-Oliver, Antonio and Torres-Anoro, Elena and Lardiés-Sanchez, Beatriz and Arbones-Mainar, Jose M. and Sanz-Paris, Alejandro and Perez-Nogueras, Javier},\\n\\tyear = {2019},\\n\\tpages = {153--157},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Serrano-Oliver, A.\",\"Torres-Anoro, E.\",\"Lardiés-Sanchez, B.\",\"Arbones-Mainar, J. M.\",\"Sanz-Paris, A.\",\"Perez-Nogueras, J.\"],\"key\":\"Serrano-Oliver2019\",\"id\":\"Serrano-Oliver2019\",\"bibbaseid\":\"serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Effects of the amino acid derivatives , β -hydroxy- β -methylbutyrate , taurine , and N-methyltyramine , on triacylglycerol breakdown in fat cells\",\"copyright\":\"All rights reserved\",\"journal\":\"Journal of Physiology and Biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Leroux\"],\"firstnames\":[\"Mélanie\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lemery\"],\"firstnames\":[\"Tristan\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Boulet\"],\"firstnames\":[\"Nathalie\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Briot\"],\"firstnames\":[\"Anaïs\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Zakaroff\"],\"firstnames\":[\"Alexia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bouloumié\"],\"firstnames\":[\"Anne\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Andrade\"],\"firstnames\":[\"Fernando\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pérez-matute\"],\"firstnames\":[\"Patricia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-mainar\"],\"firstnames\":[\"Jose\",\"M\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Carpéné\"],\"firstnames\":[\"Christian\"],\"suffixes\":[]}],\"year\":\"2019\",\"note\":\"Publisher: Journal of Physiology and Biochemistry\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view\",\"bibtex\":\"@article{Leroux2019,\\n\\ttitle = {Effects of the amino acid derivatives , β -hydroxy- β -methylbutyrate , taurine , and {N}-methyltyramine , on triacylglycerol breakdown in fat cells},\\n\\tcopyright = {All rights reserved},\\n\\tjournal = {Journal of Physiology and Biochemistry},\\n\\tauthor = {Leroux, Mélanie and Lemery, Tristan and Boulet, Nathalie and Briot, Anaïs and Zakaroff, Alexia and Bouloumié, Anne and Andrade, Fernando and Pérez-matute, Patricia and Arbones-mainar, Jose M and Carpéné, Christian},\\n\\tyear = {2019},\\n\\tnote = {Publisher: Journal of Physiology and Biochemistry},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Leroux, M.\",\"Lemery, T.\",\"Boulet, N.\",\"Briot, A.\",\"Zakaroff, A.\",\"Bouloumié, A.\",\"Andrade, F.\",\"Pérez-matute, P.\",\"Arbones-mainar, J. M\",\"Carpéné, C.\"],\"key\":\"Leroux2019\",\"id\":\"Leroux2019\",\"bibbaseid\":\"leroux-lemery-boulet-briot-zakaroff-bouloumi-andrade-prezmatute-etal-effectsoftheaminoacidderivativeshydroxymethylbutyratetaurineandnmethyltyramineontriacylglycerolbreakdowninfatcells-2019\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition\",\"copyright\":\"All rights reserved\",\"issn\":\"1138-7548\",\"url\":\"http://link.springer.com/10.1007/s13105-018-0638-9\",\"doi\":\"10.1007/s13105-018-0638-9\",\"journal\":\"Journal of Physiology and Biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Perez-Diaz\"],\"firstnames\":[\"Sergio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gonzalez-Irazabal\"],\"firstnames\":[\"Yolanda\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Rodriguez\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Espina\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arenaz\"],\"firstnames\":[\"Izaskun\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"year\":\"2018\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view\",\"bibtex\":\"@article{Perez-Diaz2018,\\n\\ttitle = {{PTRF} acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1138-7548},\\n\\turl = {http://link.springer.com/10.1007/s13105-018-0638-9},\\n\\tdoi = {10.1007/s13105-018-0638-9},\\n\\tjournal = {Journal of Physiology and Biochemistry},\\n\\tauthor = {Perez-Diaz, Sergio and Garcia-Sobreviela, Maria P. and Gonzalez-Irazabal, Yolanda and Garcia-Rodriguez, Beatriz and Espina, Silvia and Arenaz, Izaskun and Arbones-Mainar, Jose M.},\\n\\tyear = {2018},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Perez-Diaz, S.\",\"Garcia-Sobreviela, M. P.\",\"Gonzalez-Irazabal, Y.\",\"Garcia-Rodriguez, B.\",\"Espina, S.\",\"Arenaz, I.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Perez-Diaz2018\",\"id\":\"Perez-Diaz2018\",\"bibbaseid\":\"perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://link.springer.com/10.1007/s13105-018-0638-9\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice\",\"copyright\":\"All rights reserved\",\"issn\":\"18778755\",\"doi\":\"10.1007/s13105-020-00775-9\",\"abstract\":\"Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling.\",\"journal\":\"Journal of Physiology and Biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Martínez-Fernández\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"González-Muniesa\"],\"firstnames\":[\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sáinz\"],\"firstnames\":[\"N.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Escoté\"],\"firstnames\":[\"X.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martínez\"],\"firstnames\":[\"J.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moreno-Aliaga\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]}],\"year\":\"2020\",\"note\":\"Publisher: Journal of Physiology and Biochemistry\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view\",\"bibtex\":\"@article{Martinez-Fernandez2020,\\n\\ttitle = {Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {18778755},\\n\\tdoi = {10.1007/s13105-020-00775-9},\\n\\tabstract = {Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling.},\\n\\tjournal = {Journal of Physiology and Biochemistry},\\n\\tauthor = {Martínez-Fernández, L. and González-Muniesa, P. and Sáinz, N. and Escoté, X. and Martínez, J. A. and Arbones-Mainar, J. M. and Moreno-Aliaga, M. J.},\\n\\tyear = {2020},\\n\\tnote = {Publisher: Journal of Physiology and Biochemistry},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Martínez-Fernández, L.\",\"González-Muniesa, P.\",\"Sáinz, N.\",\"Escoté, X.\",\"Martínez, J. A.\",\"Arbones-Mainar, J. M.\",\"Moreno-Aliaga, M. J.\"],\"key\":\"Martinez-Fernandez2020\",\"id\":\"Martinez-Fernandez2020\",\"bibbaseid\":\"martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Post-lunch triglyceridaemia associates with HDLc and insulin resistance in fasting normotriglyceridaemic menopausal women\",\"copyright\":\"All rights reserved\",\"issn\":\"1365277X\",\"abstract\":\"© 2017 The British Dietetic Association Ltd. Objectives: Post-prandial hypertriglyceridaemia (P-HTG) is associated with cardiovascular disease. This association is of paramount importance during menopause, which is also related to reduced high-density lipoprotein-cholesterol (HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at fasting and adhered to a Mediterranean-style eating pattern. Methods: We performed oral fat loading tests (OFLT) in combination with self-measurements of diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women. TG levels \\\\textgreater 220 mg dL -1 at any given time during the OFLT served as diagnostic criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to classify these women as having P-HTG according to the OFLT. Insulin resistance was defined as the upper tertile of the homeostatic model assessment of insulin resistance. Results: We found that, despite having normal fasting TG levels, P-HTG was highly prevalent (approximately 40%). Moreover, self-assessed 3-h post-lunch TG levels \\\\textgreater 165 mg dL -1 increased the odds of having hypo-HDL cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women adhering to a Mediterranean eating pattern having their highest energy intake at lunch. Conclusions: Self-assessed 3-h post-lunch TG can be used to study post-prandial TG metabolism in Southern European menopausal women who are normotriglyceridaemic at fasting. Characterising an individual's post-prandial response may help menopausal women to evaluate their risk of cardiovascular disease.\",\"journal\":\"Journal of Human Nutrition and Dietetics\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rodriguez-Valle\"],\"firstnames\":[\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Puzo-Foncillas\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.\",\"M.\"],\"suffixes\":[]}],\"year\":\"2017\",\"doi\":\"10.1111/jhn.12476\",\"note\":\"Volume: 30 Issue: 6\",\"pages\":\"700–708\",\"bibtex\":\"@article{Sanz-Paris2017,\\n\\ttitle = {Post-lunch triglyceridaemia associates with {HDLc} and insulin resistance in fasting normotriglyceridaemic menopausal women},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1365277X},\\n\\tabstract = {© 2017 The British Dietetic Association Ltd. Objectives: Post-prandial hypertriglyceridaemia (P-HTG) is associated with cardiovascular disease. This association is of paramount importance during menopause, which is also related to reduced high-density lipoprotein-cholesterol (HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at fasting and adhered to a Mediterranean-style eating pattern. Methods: We performed oral fat loading tests (OFLT) in combination with self-measurements of diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women. TG levels {\\\\textgreater} 220 mg dL -1 at any given time during the OFLT served as diagnostic criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to classify these women as having P-HTG according to the OFLT. Insulin resistance was defined as the upper tertile of the homeostatic model assessment of insulin resistance. Results: We found that, despite having normal fasting TG levels, P-HTG was highly prevalent (approximately 40\\\\%). Moreover, self-assessed 3-h post-lunch TG levels {\\\\textgreater} 165 mg dL -1 increased the odds of having hypo-HDL cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women adhering to a Mediterranean eating pattern having their highest energy intake at lunch. Conclusions: Self-assessed 3-h post-lunch TG can be used to study post-prandial TG metabolism in Southern European menopausal women who are normotriglyceridaemic at fasting. Characterising an individual's post-prandial response may help menopausal women to evaluate their risk of cardiovascular disease.},\\n\\tjournal = {Journal of Human Nutrition and Dietetics},\\n\\tauthor = {Sanz-Paris, A. and Rodriguez-Valle, A. and Navarro, M. A. and Puzo-Foncillas, J. and Arbones-Mainar, J. M.},\\n\\tyear = {2017},\\n\\tdoi = {10.1111/jhn.12476},\\n\\tnote = {Volume: 30\\nIssue: 6},\\n\\tpages = {700--708},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Sanz-Paris, A.\",\"Rodriguez-Valle, A.\",\"Navarro, M. A.\",\"Puzo-Foncillas, J.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Sanz-Paris2017\",\"id\":\"Sanz-Paris2017\",\"bibbaseid\":\"sanzparis-rodriguezvalle-navarro-puzofoncillas-arbonesmainar-postlunchtriglyceridaemiaassociateswithhdlcandinsulinresistanceinfastingnormotriglyceridaemicmenopausalwomen-2017\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Prevalence of Malnutrition and 1-Year All-Cause Mortality in Institutionalized Elderly Patients Comparing Different Combinations of the GLIM Criteria\",\"copyright\":\"All rights reserved\",\"issn\":\"19412444\",\"doi\":\"10.1002/jpen.2029\",\"abstract\":\"Background: The Global Leadership Initiative on Malnutrition (GLIM) provided a new approach for the diagnosis of malnutrition based on a number of phenotypic and etiologic criteria. However, different diagnostic criteria could potentially lead to heterogeneity in the diagnosis. We identified different subsets of criteria to define malnutrition in a cohort of elder nursing-home residents and investigated their clinical utility in terms of 1-year survival. Methods: Our study included all residents (n = 485) from 3 nursing homes. We proposed 12 GLIM models based on different phenotypic and etiologic criteria. The main outcome was 1-year all-cause mortality. We also assessed the sensitivity and specificity for different phenotypic criteria using time-dependent receiver operating characteristic curves, and cutoff values were calculated. Results: During 1 year of follow-ups, 94 deaths occurred. The prevalence of malnutrition was 13.5% for models based on reduced food intake (RFI) and 10.45% for models based on inflammation associated with acute disease (IAD). Unadjusted Cox regression analyses showed that malnutrition was associated with a 2.31- to 4.64-fold increase in mortality when diagnosed using IAD-dependent models or with a 1.37- to 1.78-fold increase in mortality using RFI-dependent models. Cutoffs associated with mortality for the phenotypic criteria were lower than those recommended in the GLIM criteria. Conclusion: This study describes the association of several variations of the GLIM model with 1-year mortality in nursing-home residents. However, our data suggest a high heterogeneity to fulfill the GLIM criteria and the necessity of finding specific, tailored cutoff points for the studied populations.\",\"journal\":\"Journal of Parenteral and Enteral Nutrition\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"González\",\"Fernández\"],\"firstnames\":[\"Mikel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Perez-Nogueras\"],\"firstnames\":[\"Javier\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Serrano-Oliver\"],\"firstnames\":[\"Antonio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Torres-Anoro\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Arque\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"year\":\"2020\",\"pmid\":\"33043987\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view\",\"bibtex\":\"@article{Sanz-Paris2020,\\n\\ttitle = {Prevalence of {Malnutrition} and 1-{Year} {All}-{Cause} {Mortality} in {Institutionalized} {Elderly} {Patients} {Comparing} {Different} {Combinations} of the {GLIM} {Criteria}},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {19412444},\\n\\tdoi = {10.1002/jpen.2029},\\n\\tabstract = {Background: The Global Leadership Initiative on Malnutrition (GLIM) provided a new approach for the diagnosis of malnutrition based on a number of phenotypic and etiologic criteria. However, different diagnostic criteria could potentially lead to heterogeneity in the diagnosis. We identified different subsets of criteria to define malnutrition in a cohort of elder nursing-home residents and investigated their clinical utility in terms of 1-year survival. Methods: Our study included all residents (n = 485) from 3 nursing homes. We proposed 12 GLIM models based on different phenotypic and etiologic criteria. The main outcome was 1-year all-cause mortality. We also assessed the sensitivity and specificity for different phenotypic criteria using time-dependent receiver operating characteristic curves, and cutoff values were calculated. Results: During 1 year of follow-ups, 94 deaths occurred. The prevalence of malnutrition was 13.5\\\\% for models based on reduced food intake (RFI) and 10.45\\\\% for models based on inflammation associated with acute disease (IAD). Unadjusted Cox regression analyses showed that malnutrition was associated with a 2.31- to 4.64-fold increase in mortality when diagnosed using IAD-dependent models or with a 1.37- to 1.78-fold increase in mortality using RFI-dependent models. Cutoffs associated with mortality for the phenotypic criteria were lower than those recommended in the GLIM criteria. Conclusion: This study describes the association of several variations of the GLIM model with 1-year mortality in nursing-home residents. However, our data suggest a high heterogeneity to fulfill the GLIM criteria and the necessity of finding specific, tailored cutoff points for the studied populations.},\\n\\tjournal = {Journal of Parenteral and Enteral Nutrition},\\n\\tauthor = {Sanz-Paris, Alejandro and González Fernández, Mikel and Perez-Nogueras, Javier and Serrano-Oliver, Antonio and Torres-Anoro, Elena and Sanz-Arque, Alejandro and Arbones-Mainar, Jose M.},\\n\\tyear = {2020},\\n\\tpmid = {33043987},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Sanz-Paris, A.\",\"González Fernández, M.\",\"Perez-Nogueras, J.\",\"Serrano-Oliver, A.\",\"Torres-Anoro, E.\",\"Sanz-Arque, A.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Sanz-Paris2020\",\"id\":\"Sanz-Paris2020\",\"bibbaseid\":\"sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects\",\"copyright\":\"All rights reserved\",\"issn\":\"1138-7548\",\"url\":\"http://link.springer.com/10.1007/s13105-015-0464-2\",\"doi\":\"10.1007/s13105-015-0464-2\",\"number\":\"72\",\"journal\":\"Journal of physiology and biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Hijona\"],\"firstnames\":[\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aguirre\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pérez-Matute\"],\"firstnames\":[\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Villanueva-Millán\"],\"firstnames\":[\"M.\",\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Mosqueda-Solis\"],\"firstnames\":[\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hasnaoui\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Nepveu\"],\"firstnames\":[\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Senard\"],\"firstnames\":[\"J.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bujanda\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldámiz-Echevarría\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Llarena\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Andrade\"],\"firstnames\":[\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Perio\"],\"firstnames\":[\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Leboulanger\"],\"firstnames\":[\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hijona\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Portillo\"],\"firstnames\":[\"M.P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Carpéné\"],\"firstnames\":[\"C.\"],\"suffixes\":[]}],\"year\":\"2016\",\"note\":\"Publisher: Springer Netherlands\",\"pages\":\"567–582\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view\",\"bibtex\":\"@article{Hijona2016a,\\n\\ttitle = {Limited beneficial effects of piceatannol supplementation on obesity complications in the obese {Zucker} rat: gut microbiota, metabolic, endocrine, and cardiac aspects},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1138-7548},\\n\\turl = {http://link.springer.com/10.1007/s13105-015-0464-2},\\n\\tdoi = {10.1007/s13105-015-0464-2},\\n\\tnumber = {72},\\n\\tjournal = {Journal of physiology and biochemistry},\\n\\tauthor = {Hijona, E. and Aguirre, L. and Pérez-Matute, P. and Villanueva-Millán, M. J. and Mosqueda-Solis, A. and Hasnaoui, M. and Nepveu, F. and Senard, J. M. and Bujanda, L. and Aldámiz-Echevarría, L. and Llarena, M. and Andrade, F. and Perio, P. and Leboulanger, F. and Hijona, L. and Arbones-Mainar, J. M. and Portillo, M.P. and Carpéné, C.},\\n\\tyear = {2016},\\n\\tnote = {Publisher: Springer Netherlands},\\n\\tpages = {567--582},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Hijona, E.\",\"Aguirre, L.\",\"Pérez-Matute, P.\",\"Villanueva-Millán, M. J.\",\"Mosqueda-Solis, A.\",\"Hasnaoui, M.\",\"Nepveu, F.\",\"Senard, J. M.\",\"Bujanda, L.\",\"Aldámiz-Echevarría, L.\",\"Llarena, M.\",\"Andrade, F.\",\"Perio, P.\",\"Leboulanger, F.\",\"Hijona, L.\",\"Arbones-Mainar, J. M.\",\"Portillo, M.\",\"Carpéné, C.\"],\"key\":\"Hijona2016a\",\"id\":\"Hijona2016a\",\"bibbaseid\":\"hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://link.springer.com/10.1007/s13105-015-0464-2\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.\",\"volume\":\"28\",\"copyright\":\"All rights reserved\",\"issn\":\"1530-6860\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/24812087\",\"doi\":\"10.1096/fj.14-251165\",\"abstract\":\"Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management.-Perez-Diaz, S., Johnson, L. A., DeKroon, R. M., Moreno-Navarrete, J. M., Alzate, O., Fernandez-Real, J. M., Maeda, N., Arbones-Mainar, J. M. Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.\",\"urldate\":\"2014-05-15\",\"journal\":\"FASEB journal\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Perez-Diaz\"],\"firstnames\":[\"Sergio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"Lance\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"DeKroon\"],\"firstnames\":[\"Robert\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moreno-Navarrete\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Alzate\"],\"firstnames\":[\"Oscar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Fernandez-Real\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"Nobuyo\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"May\",\"year\":\"2014\",\"pmid\":\"24812087\",\"pages\":\"1–11\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view\",\"bibtex\":\"@article{Perez-Diaz2014b,\\n\\ttitle = {Polymerase {I} and transcript release factor ({PTRF}) regulates adipocyte differentiation and determines adipose tissue expandability.},\\n\\tvolume = {28},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1530-6860},\\n\\turl = {http://www.ncbi.nlm.nih.gov/pubmed/24812087},\\n\\tdoi = {10.1096/fj.14-251165},\\n\\tabstract = {Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management.-Perez-Diaz, S., Johnson, L. A., DeKroon, R. M., Moreno-Navarrete, J. M., Alzate, O., Fernandez-Real, J. M., Maeda, N., Arbones-Mainar, J. M. Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.},\\n\\turldate = {2014-05-15},\\n\\tjournal = {FASEB journal},\\n\\tauthor = {Perez-Diaz, Sergio and Johnson, Lance A. and DeKroon, Robert M. and Moreno-Navarrete, Jose M. and Alzate, Oscar and Fernandez-Real, Jose M. and Maeda, Nobuyo and Arbones-Mainar, Jose M.},\\n\\tmonth = may,\\n\\tyear = {2014},\\n\\tpmid = {24812087},\\n\\tpages = {1--11},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Perez-Diaz, S.\",\"Johnson, L. A.\",\"DeKroon, R. M.\",\"Moreno-Navarrete, J. M.\",\"Alzate, O.\",\"Fernandez-Real, J. M.\",\"Maeda, N.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Perez-Diaz2014b\",\"id\":\"Perez-Diaz2014b\",\"bibbaseid\":\"perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/24812087\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"ALTERACIONES DEL METABOLISMO LIPÍDICO PRODUCIDAS POR EL VIRUS DE LA HEPATITIS C EN PACIENTES CON INFECCIÓN CRÓNICA\",\"volume\":\"94\",\"copyright\":\"All rights reserved\",\"journal\":\"Rev Esp Salud Pública\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Muñoz-Cabrejas\"],\"firstnames\":[\"Ainara\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Espina-Cadena\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"José\",\"Miguel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moreno-Franco\"],\"firstnames\":[\"Belén\"],\"suffixes\":[]}],\"year\":\"2020\",\"pages\":\"e1–15\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view\",\"bibtex\":\"@article{Munoz-Cabrejas2020,\\n\\ttitle = {{ALTERACIONES} {DEL} {METABOLISMO} {LIPÍDICO} {PRODUCIDAS} {POR} {EL} {VIRUS} {DE} {LA} {HEPATITIS} {C} {EN} {PACIENTES} {CON} {INFECCIÓN} {CRÓNICA}},\\n\\tvolume = {94},\\n\\tcopyright = {All rights reserved},\\n\\tjournal = {Rev Esp Salud Pública},\\n\\tauthor = {Muñoz-Cabrejas, Ainara and Espina-Cadena, Silvia and Arbones-Mainar, José Miguel and Moreno-Franco, Belén},\\n\\tyear = {2020},\\n\\tpages = {e1--15},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Muñoz-Cabrejas, A.\",\"Espina-Cadena, S.\",\"Arbones-Mainar, J. M.\",\"Moreno-Franco, B.\"],\"key\":\"Munoz-Cabrejas2020\",\"id\":\"Munoz-Cabrejas2020\",\"bibbaseid\":\"muozcabrejas-espinacadena-arbonesmainar-morenofranco-alteracionesdelmetabolismolipdicoproducidasporelvirusdelahepatitiscenpacientesconinfeccincrnica-2020\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Beyond the CNS: The many peripheral roles of APOE.\",\"volume\":\"138\",\"copyright\":\"All rights reserved\",\"issn\":\"1095-953X\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/32087284\",\"doi\":\"10.1016/j.nbd.2020.104809\",\"abstract\":\"Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.\",\"number\":\"November 2019\",\"journal\":\"Neurobiology of disease\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Martinez-Martínez\"],\"firstnames\":[\"Ana\",\"B\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Torres-Perez\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Devanney\"],\"firstnames\":[\"Nicholas\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Del\",\"Moral\"],\"firstnames\":[\"Raquel\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"Lance\",\"A\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M\"],\"suffixes\":[]}],\"year\":\"2020\",\"pmid\":\"32087284\",\"note\":\"Publisher: Elsevier\",\"pages\":\"104809\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view\",\"bibtex\":\"@article{Martinez-Martinez2020,\\n\\ttitle = {Beyond the {CNS}: {The} many peripheral roles of {APOE}.},\\n\\tvolume = {138},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1095-953X},\\n\\turl = {http://www.ncbi.nlm.nih.gov/pubmed/32087284},\\n\\tdoi = {10.1016/j.nbd.2020.104809},\\n\\tabstract = {Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75\\\\% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.},\\n\\tnumber = {November 2019},\\n\\tjournal = {Neurobiology of disease},\\n\\tauthor = {Martinez-Martínez, Ana B and Torres-Perez, Elena and Devanney, Nicholas and Del Moral, Raquel and Johnson, Lance A and Arbones-Mainar, Jose M},\\n\\tyear = {2020},\\n\\tpmid = {32087284},\\n\\tnote = {Publisher: Elsevier},\\n\\tpages = {104809},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Martinez-Martínez, A. B\",\"Torres-Perez, E.\",\"Devanney, N.\",\"Del Moral, R.\",\"Johnson, L. A\",\"Arbones-Mainar, J. M\"],\"key\":\"Martinez-Martinez2020\",\"id\":\"Martinez-Martinez2020\",\"bibbaseid\":\"martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/32087284\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Apolipoprotein E4 Exaggerates Diabetic Dyslipidemia and Atherosclerosis in Mice Lacking the LDL Receptor.\",\"volume\":\"60\",\"copyright\":\"All rights reserved\",\"issn\":\"1939-327X\",\"url\":\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&tool=pmcentrez&rendertype=abstract\",\"doi\":\"10.2337/db11-0466\",\"abstract\":\"OBJECTIVE We investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia-a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR(-/-)). RESULTS Diabetic E3LDLR(-/-) and E4LDLR(-/-) mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR(-/-) mice twice as much as in E3LDLR(-/-) mice. Diabetic E4LDLR(-/-) mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR(-/-) mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR(-/-) mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR(-/-) primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR(-/-) hepatocytes concomitant with a 60% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR(-/-) mice was accompanied by a dramatic increase in atherosclerosis. CONCLUSIONS ApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.\",\"number\":\"9\",\"urldate\":\"2011-09-13\",\"journal\":\"Diabetes\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"Lance\",\"A\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Fox\"],\"firstnames\":[\"Raymond\",\"G\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pendse\"],\"firstnames\":[\"Avani\",\"A\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Altenburg\"],\"firstnames\":[\"Michael\",\"K\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Kim\"],\"firstnames\":[\"Hyung-Suk\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"Nobuyo\"],\"suffixes\":[]}],\"month\":\"September\",\"year\":\"2011\",\"pmid\":\"21810592\",\"pages\":\"2285–94\",\"bibtex\":\"@article{Johnson2011,\\n\\ttitle = {Apolipoprotein {E4} {Exaggerates} {Diabetic} {Dyslipidemia} and {Atherosclerosis} in {Mice} {Lacking} the {LDL} {Receptor}.},\\n\\tvolume = {60},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1939-327X},\\n\\turl = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&tool=pmcentrez&rendertype=abstract},\\n\\tdoi = {10.2337/db11-0466},\\n\\tabstract = {OBJECTIVE We investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia-a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR(-/-)). RESULTS Diabetic E3LDLR(-/-) and E4LDLR(-/-) mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR(-/-) mice twice as much as in E3LDLR(-/-) mice. Diabetic E4LDLR(-/-) mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR(-/-) mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR(-/-) mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR(-/-) primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR(-/-) hepatocytes concomitant with a 60\\\\% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR(-/-) mice was accompanied by a dramatic increase in atherosclerosis. CONCLUSIONS ApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.},\\n\\tnumber = {9},\\n\\turldate = {2011-09-13},\\n\\tjournal = {Diabetes},\\n\\tauthor = {Johnson, Lance A and Arbones-Mainar, Jose M and Fox, Raymond G and Pendse, Avani A and Altenburg, Michael K and Kim, Hyung-Suk and Maeda, Nobuyo},\\n\\tmonth = sep,\\n\\tyear = {2011},\\n\\tpmid = {21810592},\\n\\tpages = {2285--94},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Johnson, L. A\",\"Arbones-Mainar, J. M\",\"Fox, R. G\",\"Pendse, A. A\",\"Altenburg, M. K\",\"Kim, H.\",\"Maeda, N.\"],\"key\":\"Johnson2011\",\"id\":\"Johnson2011\",\"bibbaseid\":\"johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&tool=pmcentrez&rendertype=abstract\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice\",\"volume\":\"32\",\"copyright\":\"All rights reserved\",\"issn\":\"03070565\",\"doi\":\"10.1038/ijo.2008.143\",\"abstract\":\"Objective: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly expressed in adipose tissues. Studies have shown that human APOE*4 is associated with a lower body mass index but with a greater risk of coronary heart disease compared with other APOE alleles. To define the isoform-specific role of apoE in regulating the expandability and functionality of adipose tissues, we investigated the effects of diet-induced obesity in mice whose endogenous Apoe gene has been replaced by either the human APOE*3 or APOE*4 allele. Results: After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed impaired tolerance to glucose and fat overload compared with APOE3 mice. Subcutaneous fat tissues in APOE4 and APOE3 mice after high fat feeding were not different. In contrast, although epididymal fat tissues in APOE4 mice gained 30% less weight during the high fat feeding than in APOE3 mice, they showed impaired insulin-stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were larger in size than APOE3 adipocytes, and expressed reduced levels of mRNA for peroxisome proliferator-activated receptor γ2 and adiponectin, important markers of adipocyte functionality. Adenoviral expression of apoE3 in apoE-null culture adipocytes induced adiponectin mRNA in a dose-dependent manner, but the induction was significantly blunted in cells overexpressing apoE4. However, in contrast to the apoE3-expressing cells, Glut1, but not Glut4, expression levels were positively correlated with increased apoE4 mRNA, suggesting that apoE4 expression in adipocyte interferes in insulin-sensing pathways. Conclusion: Dysfunctional epididymal adipose tissues contribute to the accelerated impairment of glucose tolerance in APOE4 mice fed a Western-type diet. Our results underscore the importance of functionality of individual fat depots rather than total fat mass as a determinant for metabolic disturbance during diet-induced obesity. © 2008 Macmillan Publishers Limited All rights reserved.\",\"number\":\"10\",\"journal\":\"International Journal of Obesity\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"L.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Altenburg\"],\"firstnames\":[\"M.K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"N.\"],\"suffixes\":[]}],\"year\":\"2008\",\"bibtex\":\"@article{arbones-mainar_differential_2008,\\n\\ttitle = {Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein {E3} and {E4} in mice},\\n\\tvolume = {32},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {03070565},\\n\\tdoi = {10.1038/ijo.2008.143},\\n\\tabstract = {Objective: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly expressed in adipose tissues. Studies have shown that human APOE*4 is associated with a lower body mass index but with a greater risk of coronary heart disease compared with other APOE alleles. To define the isoform-specific role of apoE in regulating the expandability and functionality of adipose tissues, we investigated the effects of diet-induced obesity in mice whose endogenous Apoe gene has been replaced by either the human APOE*3 or APOE*4 allele. Results: After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed impaired tolerance to glucose and fat overload compared with APOE3 mice. Subcutaneous fat tissues in APOE4 and APOE3 mice after high fat feeding were not different. In contrast, although epididymal fat tissues in APOE4 mice gained 30\\\\% less weight during the high fat feeding than in APOE3 mice, they showed impaired insulin-stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were larger in size than APOE3 adipocytes, and expressed reduced levels of mRNA for peroxisome proliferator-activated receptor γ2 and adiponectin, important markers of adipocyte functionality. Adenoviral expression of apoE3 in apoE-null culture adipocytes induced adiponectin mRNA in a dose-dependent manner, but the induction was significantly blunted in cells overexpressing apoE4. However, in contrast to the apoE3-expressing cells, Glut1, but not Glut4, expression levels were positively correlated with increased apoE4 mRNA, suggesting that apoE4 expression in adipocyte interferes in insulin-sensing pathways. Conclusion: Dysfunctional epididymal adipose tissues contribute to the accelerated impairment of glucose tolerance in APOE4 mice fed a Western-type diet. Our results underscore the importance of functionality of individual fat depots rather than total fat mass as a determinant for metabolic disturbance during diet-induced obesity. © 2008 Macmillan Publishers Limited All rights reserved.},\\n\\tnumber = {10},\\n\\tjournal = {International Journal of Obesity},\\n\\tauthor = {Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Maeda, N.},\\n\\tyear = {2008},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Arbones-Mainar, J.\",\"Johnson, L.\",\"Altenburg, M.\",\"Maeda, N.\"],\"key\":\"arbones-mainar_differential_2008\",\"id\":\"arbones-mainar_differential_2008\",\"bibbaseid\":\"arbonesmainar-johnson-altenburg-maeda-differentialmodulationofdietinducedobesityandadipocytefunctionalitybyhumanapolipoproteine3ande4inmice-2008\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Understanding the role of dietary components on atherosclerosis using genetic engineered mouse models\",\"volume\":\"11\",\"copyright\":\"All rights reserved\",\"issn\":\"10939946\",\"doi\":\"10.2741/1852\",\"abstract\":\"The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoicing potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.\",\"number\":\"1 P.889-1198\",\"journal\":\"Frontiers in Bioscience\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Sarria\"],\"firstnames\":[\"A.J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Surra\"],\"firstnames\":[\"J.C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Acin\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Carnicer\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Guillen\"],\"firstnames\":[\"N.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martinez-Gracia\"],\"firstnames\":[\"M.V.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arnal\"],\"firstnames\":[\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Osada\"],\"firstnames\":[\"J.\"],\"suffixes\":[]}],\"year\":\"2006\",\"bibtex\":\"@article{sarria_understanding_2006,\\n\\ttitle = {Understanding the role of dietary components on atherosclerosis using genetic engineered mouse models},\\n\\tvolume = {11},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {10939946},\\n\\tdoi = {10.2741/1852},\\n\\tabstract = {The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoicing potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.},\\n\\tnumber = {1 P.889-1198},\\n\\tjournal = {Frontiers in Bioscience},\\n\\tauthor = {Sarria, A.J. and Surra, J.C. and Acin, S. and Carnicer, R. and Navarro, M.A. and Arbones-Mainar, J.M. and Guillen, N. and Martinez-Gracia, M.V. and Arnal, C. and Osada, J.},\\n\\tyear = {2006},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Sarria, A.\",\"Surra, J.\",\"Acin, S.\",\"Carnicer, R.\",\"Navarro, M.\",\"Arbones-Mainar, J.\",\"Guillen, N.\",\"Martinez-Gracia, M.\",\"Arnal, C.\",\"Osada, J.\"],\"key\":\"sarria_understanding_2006\",\"id\":\"sarria_understanding_2006\",\"bibbaseid\":\"sarria-surra-acin-carnicer-navarro-arbonesmainar-guillen-martinezgracia-etal-understandingtheroleofdietarycomponentsonatherosclerosisusinggeneticengineeredmousemodels-2006\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Folic acid supplementation delays atherosclerotic lesion development in apoE-deficient mice\",\"volume\":\"19\",\"copyright\":\"All rights reserved\",\"issn\":\"15781879\",\"doi\":\"10.1016/S0214-9168(07)74181-5\",\"number\":\"2\",\"journal\":\"Clinica e Investigacion en Arteriosclerosis\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Carnicer\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Acin\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Guzman\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Surra\"],\"firstnames\":[\"J.C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arnal\"],\"firstnames\":[\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"De\",\"Las\",\"Heras\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Blanco-Vaca\"],\"firstnames\":[\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Osada\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Antonia\",\"Vilaseca\"],\"firstnames\":[\"M.\"],\"suffixes\":[]}],\"year\":\"2007\",\"bibtex\":\"@article{carnicer_folic_2007,\\n\\ttitle = {Folic acid supplementation delays atherosclerotic lesion development in {apoE}-deficient mice},\\n\\tvolume = {19},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {15781879},\\n\\tdoi = {10.1016/S0214-9168(07)74181-5},\\n\\tnumber = {2},\\n\\tjournal = {Clinica e Investigacion en Arteriosclerosis},\\n\\tauthor = {Carnicer, R. and Navarro, M. and Arbones-Mainar, J.M. and Acin, S. and Guzman, M.A. and Surra, J.C. and Arnal, C. and De Las Heras, M. and Blanco-Vaca, F. and Osada, J. and Antonia Vilaseca, M.},\\n\\tyear = {2007},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Carnicer, R.\",\"Navarro, M.\",\"Arbones-Mainar, J.\",\"Acin, S.\",\"Guzman, M.\",\"Surra, J.\",\"Arnal, C.\",\"De Las Heras, M.\",\"Blanco-Vaca, F.\",\"Osada, J.\",\"Antonia Vilaseca, M.\"],\"key\":\"carnicer_folic_2007\",\"id\":\"carnicer_folic_2007\",\"bibbaseid\":\"carnicer-navarro-arbonesmainar-acin-guzman-surra-arnal-delasheras-etal-folicacidsupplementationdelaysatheroscleroticlesiondevelopmentinapoedeficientmice-2007\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity\",\"volume\":\"14\",\"copyright\":\"All rights reserved\",\"issn\":\"1475-2840\",\"url\":\"http://www.cardiab.com/content/14/1/40\",\"doi\":\"10.1186/s12933-015-0203-6\",\"abstract\":\"BACKGROUND:Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.METHODS/DESIGN:FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance.DISCUSSION:The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.\",\"number\":\"1\",\"journal\":\"Cardiovascular Diabetology\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Torres-Perez\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Valero\"],\"firstnames\":[\"Monica\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Rodriguez\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gonzalez-Irazabal\"],\"firstnames\":[\"Yolanda\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Calmarza\"],\"firstnames\":[\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Calvo-Ruata\"],\"firstnames\":[\"Luisa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ortega\"],\"firstnames\":[\"Carmen\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Artigas\"],\"firstnames\":[\"Jose\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lagos\"],\"firstnames\":[\"Javier\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\"],\"suffixes\":[]}],\"year\":\"2015\",\"pages\":\"40\",\"bibtex\":\"@article{Torres-Perez2015,\\n\\ttitle = {The {FAT} expandability ({FATe}) {Project}: {Biomarkers} to determine the limit of expansion and the complications of obesity},\\n\\tvolume = {14},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1475-2840},\\n\\turl = {http://www.cardiab.com/content/14/1/40},\\n\\tdoi = {10.1186/s12933-015-0203-6},\\n\\tabstract = {BACKGROUND:Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.METHODS/DESIGN:FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance.DISCUSSION:The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.},\\n\\tnumber = {1},\\n\\tjournal = {Cardiovascular Diabetology},\\n\\tauthor = {Torres-Perez, Elena and Valero, Monica and Garcia-Rodriguez, Beatriz and Gonzalez-Irazabal, Yolanda and Calmarza, Pilar and Calvo-Ruata, Luisa and Ortega, Carmen and Garcia-Sobreviela, Maria and Sanz-Paris, Alejandro and Artigas, Jose and Lagos, Javier and Arbones-Mainar, Jose},\\n\\tyear = {2015},\\n\\tpages = {40},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Torres-Perez, E.\",\"Valero, M.\",\"Garcia-Rodriguez, B.\",\"Gonzalez-Irazabal, Y.\",\"Calmarza, P.\",\"Calvo-Ruata, L.\",\"Ortega, C.\",\"Garcia-Sobreviela, M.\",\"Sanz-Paris, A.\",\"Artigas, J.\",\"Lagos, J.\",\"Arbones-Mainar, J.\"],\"key\":\"Torres-Perez2015\",\"id\":\"Torres-Perez2015\",\"bibbaseid\":\"torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.cardiab.com/content/14/1/40\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in APOE$^{\\\\textrm{-/-}}$mice\",\"volume\":\"6\",\"copyright\":\"All rights reserved\",\"issn\":\"15353893\",\"doi\":\"10.1021/pr070321a\",\"abstract\":\"We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe -/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p \\\\textless 0.05), though Picual olive oil significantly decreased plasma triglycerides (p \\\\textless 0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our \\\"systems biology\\\" approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti-atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis. © 2007 American Chemical Society.\",\"number\":\"10\",\"journal\":\"Journal of Proteome Research\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ross\"],\"firstnames\":[\"K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rucklidge\"],\"firstnames\":[\"G.J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Reid\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Duncan\"],\"firstnames\":[\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arthur\"],\"firstnames\":[\"J.R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Horgan\"],\"firstnames\":[\"G.W.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Carnicer\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arnal\"],\"firstnames\":[\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Osada\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"De\",\"Roos\"],\"firstnames\":[\"B.\"],\"suffixes\":[]}],\"year\":\"2007\",\"bibtex\":\"@article{arbones-mainar_extra_2007,\\n\\ttitle = {Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in {APOE}$^{\\\\textrm{-/-}}$mice},\\n\\tvolume = {6},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {15353893},\\n\\tdoi = {10.1021/pr070321a},\\n\\tabstract = {We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe -/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p  {\\\\textless}  0.05), though Picual olive oil significantly decreased plasma triglycerides (p  {\\\\textless}  0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our \\\"systems biology\\\" approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti-atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis. © 2007 American Chemical Society.},\\n\\tnumber = {10},\\n\\tjournal = {Journal of Proteome Research},\\n\\tauthor = {Arbones-Mainar, J.M. and Ross, K. and Rucklidge, G.J. and Reid, M. and Duncan, G. and Arthur, J.R. and Horgan, G.W. and Navarro, M.A. and Carnicer, R. and Arnal, C. and Osada, J. and De Roos, B.},\\n\\tyear = {2007},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Arbones-Mainar, J.\",\"Ross, K.\",\"Rucklidge, G.\",\"Reid, M.\",\"Duncan, G.\",\"Arthur, J.\",\"Horgan, G.\",\"Navarro, M.\",\"Carnicer, R.\",\"Arnal, C.\",\"Osada, J.\",\"De Roos, B.\"],\"key\":\"arbones-mainar_extra_2007\",\"id\":\"arbones-mainar_extra_2007\",\"bibbaseid\":\"arbonesmainar-ross-rucklidge-reid-duncan-arthur-horgan-navarro-etal-extravirginoliveoilsincreasehepaticfataccumulationandhepaticantioxidantproteinlevelsinapoetextrmmice-2007\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome\",\"volume\":\"13\",\"copyright\":\"All rights reserved\",\"issn\":\"22132317\",\"doi\":\"10.1016/j.redox.2017.05.026\",\"abstract\":\"© 2017 The Authors The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.\",\"journal\":\"Redox Biology\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Llobet\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Bayona-Bafaluy\"],\"firstnames\":[\"M.P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pacheu-Grau\"],\"firstnames\":[\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Torres-Pérez\"],\"firstnames\":[\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.Á.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gómez-Díaz\"],\"firstnames\":[\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Montoya\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"López-Gallardo\"],\"firstnames\":[\"E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ruiz-Pesini\"],\"firstnames\":[\"E.\"],\"suffixes\":[]}],\"year\":\"2017\",\"bibtex\":\"@article{Llobet2017,\\n\\ttitle = {Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome},\\n\\tvolume = {13},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {22132317},\\n\\tdoi = {10.1016/j.redox.2017.05.026},\\n\\tabstract = {© 2017 The Authors The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.},\\n\\tjournal = {Redox Biology},\\n\\tauthor = {Llobet, L. and Bayona-Bafaluy, M.P. and Pacheu-Grau, D. and Torres-Pérez, E. and Arbones-Mainar, J.M. and Navarro, M.Á. and Gómez-Díaz, C. and Montoya, J. and López-Gallardo, E. and Ruiz-Pesini, E.},\\n\\tyear = {2017},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Llobet, L.\",\"Bayona-Bafaluy, M.\",\"Pacheu-Grau, D.\",\"Torres-Pérez, E.\",\"Arbones-Mainar, J.\",\"Navarro, M.\",\"Gómez-Díaz, C.\",\"Montoya, J.\",\"López-Gallardo, E.\",\"Ruiz-Pesini, E.\"],\"key\":\"Llobet2017\",\"id\":\"Llobet2017\",\"bibbaseid\":\"llobet-bayonabafaluy-pacheugrau-torresprez-arbonesmainar-navarro-gmezdaz-montoya-etal-pharmacologicconcentrationsoflinezolidmodifyoxidativephosphorylationfunctionandadipocytesecretome-2017\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: A proteomics approach\",\"volume\":\"19\",\"copyright\":\"All rights reserved\",\"issn\":\"08926638\",\"doi\":\"10.1096/fj.05-3953fje\",\"number\":\"12\",\"journal\":\"FASEB Journal\",\"author\":[{\"propositions\":[],\"lastnames\":[\"De\",\"Roos\"],\"firstnames\":[\"B.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Rucklidge\"],\"firstnames\":[\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Reid\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ross\"],\"firstnames\":[\"K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Duncan\"],\"firstnames\":[\"G.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Guzman-Garcia\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Osada\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Browne\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Loscher\"],\"firstnames\":[\"C.E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Roche\"],\"firstnames\":[\"H.M.\"],\"suffixes\":[]}],\"year\":\"2005\",\"bibtex\":\"@article{de_roos_divergent_2005,\\n\\ttitle = {Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein {E} knockout mice: {A} proteomics approach},\\n\\tvolume = {19},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {08926638},\\n\\tdoi = {10.1096/fj.05-3953fje},\\n\\tnumber = {12},\\n\\tjournal = {FASEB Journal},\\n\\tauthor = {De Roos, B. and Rucklidge, G. and Reid, M. and Ross, K. and Duncan, G. and Navarro, M.A. and Arbones-Mainar, J.M. and Guzman-Garcia, M.A. and Osada, J. and Browne, J. and Loscher, C.E. and Roche, H.M.},\\n\\tyear = {2005},\\n}\\n\\n\\n\\n\",\"author_short\":[\"De Roos, B.\",\"Rucklidge, G.\",\"Reid, M.\",\"Ross, K.\",\"Duncan, G.\",\"Navarro, M.\",\"Arbones-Mainar, J.\",\"Guzman-Garcia, M.\",\"Osada, J.\",\"Browne, J.\",\"Loscher, C.\",\"Roche, H.\"],\"key\":\"de_roos_divergent_2005\",\"id\":\"de_roos_divergent_2005\",\"bibbaseid\":\"deroos-rucklidge-reid-ross-duncan-navarro-arbonesmainar-guzmangarcia-etal-divergentmechanismsofcis9trans11andtrans10cis12conjugatedlinoleicacidaffectinginsulinresistanceandinflammationinapolipoproteineknockoutmiceaproteomicsapproach-2005\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men.\",\"volume\":\"9\",\"copyright\":\"All rights reserved\",\"issn\":\"1932-6203\",\"url\":\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&tool=pmcentrez&rendertype=abstract\",\"doi\":\"10.1371/journal.pone.0108605\",\"abstract\":\"BACKGROUND: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined. METHODS: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease. RESULTS: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI\\\\textgreater30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01-1.59). CONCLUSIONS: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.\",\"number\":\"9\",\"urldate\":\"2014-11-11\",\"journal\":\"PloS one\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Tejedor\"],\"firstnames\":[\"M\",\"Teresa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ledesma\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M\"],\"suffixes\":[]}],\"month\":\"January\",\"year\":\"2014\",\"pmid\":\"25268647\",\"pages\":\"e108605\",\"bibtex\":\"@article{Tejedor2014,\\n\\ttitle = {The {Apolipoprotein} {E} {Polymorphism} rs7412 {Associates} with {Body} {Fatness} {Independently} of {Plasma} {Lipids} in {Middle} {Aged} {Men}.},\\n\\tvolume = {9},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1932-6203},\\n\\turl = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&tool=pmcentrez&rendertype=abstract},\\n\\tdoi = {10.1371/journal.pone.0108605},\\n\\tabstract = {BACKGROUND: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.\\n\\nMETHODS: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.\\n\\nRESULTS: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI{\\\\textgreater}30) for individuals carrying the APOε2 allele, present in 14\\\\% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95\\\\% CI: 1.01-1.59).\\n\\nCONCLUSIONS: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.},\\n\\tnumber = {9},\\n\\turldate = {2014-11-11},\\n\\tjournal = {PloS one},\\n\\tauthor = {Tejedor, M Teresa and Garcia-Sobreviela, Maria Pilar and Ledesma, Marta and Arbones-Mainar, Jose M},\\n\\tmonth = jan,\\n\\tyear = {2014},\\n\\tpmid = {25268647},\\n\\tpages = {e108605},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Tejedor, M T.\",\"Garcia-Sobreviela, M. P.\",\"Ledesma, M.\",\"Arbones-Mainar, J. M\"],\"key\":\"Tejedor2014\",\"id\":\"Tejedor2014\",\"bibbaseid\":\"tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&tool=pmcentrez&rendertype=abstract\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"book\",\"type\":\"book\",\"title\":\"The Effects of Olive Oils on Hepatic Lipid Metabolism and Antioxidant Defense Mechanisms: Insights from Proteomics Studies\",\"copyright\":\"All rights reserved\",\"isbn\":\"978-0-12-374420-3\",\"abstract\":\"Olive oil is a natural juice of the olive fruit, and it is a major fat source in the Mediterranean diet. Although this diet is associated with a lower rate of coronary heart disease (CHD), as well as a reduction in all-cause mortality, data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. The Mediterranean diet might protect against coronary heart disease through improvement of the lipoprotein profile, improvement of the postprandial pro-thrombotic profile, lowering of blood pressure, and an improvement in insulin sensitivity both in healthy and in type 2 diabetic patients. These potential beneficial effects of olive oil suggest that its consumption affects hepatic lipid and glucose metabolism. Effects of olive oil on health may be due to both its high content of mono-unsaturated fatty acids or alternatively, due to its polar, minor components, which are rich in antioxidant phenolics. As natural dietary antioxidants, these phenolic compounds may protect the organism against damage caused by oxidant agents like active oxygen species and free radicals. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved.\",\"author\":[{\"propositions\":[],\"lastnames\":[\"De\",\"Roos\"],\"firstnames\":[\"B.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gutiérrez\"],\"firstnames\":[\"G.R.\"],\"suffixes\":[]}],\"year\":\"2010\",\"doi\":\"10.1016/B978-0-12-374420-3.00095-4\",\"note\":\"Publication Title: Olives and Olive Oil in Health and Disease Prevention\",\"bibtex\":\"@book{de_roos_effects_2010,\\n\\ttitle = {The {Effects} of {Olive} {Oils} on {Hepatic} {Lipid} {Metabolism} and {Antioxidant} {Defense} {Mechanisms}: {Insights} from {Proteomics} {Studies}},\\n\\tcopyright = {All rights reserved},\\n\\tisbn = {978-0-12-374420-3},\\n\\tabstract = {Olive oil is a natural juice of the olive fruit, and it is a major fat source in the Mediterranean diet. Although this diet is associated with a lower rate of coronary heart disease (CHD), as well as a reduction in all-cause mortality, data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. The Mediterranean diet might protect against coronary heart disease through improvement of the lipoprotein profile, improvement of the postprandial pro-thrombotic profile, lowering of blood pressure, and an improvement in insulin sensitivity both in healthy and in type 2 diabetic patients. These potential beneficial effects of olive oil suggest that its consumption affects hepatic lipid and glucose metabolism. Effects of olive oil on health may be due to both its high content of mono-unsaturated fatty acids or alternatively, due to its polar, minor components, which are rich in antioxidant phenolics. As natural dietary antioxidants, these phenolic compounds may protect the organism against damage caused by oxidant agents like active oxygen species and free radicals. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved.},\\n\\tauthor = {De Roos, B. and Arbones-Mainar, J.M. and Gutiérrez, G.R.},\\n\\tyear = {2010},\\n\\tdoi = {10.1016/B978-0-12-374420-3.00095-4},\\n\\tnote = {Publication Title: Olives and Olive Oil in Health and Disease Prevention},\\n}\\n\\n\\n\\n\",\"author_short\":[\"De Roos, B.\",\"Arbones-Mainar, J.\",\"Gutiérrez, G.\"],\"key\":\"de_roos_effects_2010\",\"id\":\"de_roos_effects_2010\",\"bibbaseid\":\"deroos-arbonesmainar-gutirrez-theeffectsofoliveoilsonhepaticlipidmetabolismandantioxidantdefensemechanismsinsightsfromproteomicsstudies-2010\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Genetic background in apolipoprotein A-I and cystathionine β-synthase deficiency\",\"volume\":\"13\",\"copyright\":\"All rights reserved\",\"issn\":\"10939946\",\"doi\":\"10.2741/3071\",\"abstract\":\"Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.\",\"number\":\"13\",\"journal\":\"Frontiers in Bioscience\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Carnicer\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Guzman\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Acin\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Surra\"],\"firstnames\":[\"J.C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Navarro\"],\"firstnames\":[\"M.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arnal\"],\"firstnames\":[\"C.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Morales\"],\"firstnames\":[\"R.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Osada\"],\"firstnames\":[\"J.\"],\"suffixes\":[]}],\"year\":\"2008\",\"bibtex\":\"@article{carnicer_genetic_2008,\\n\\ttitle = {Genetic background in apolipoprotein {A}-{I} and cystathionine β-synthase deficiency},\\n\\tvolume = {13},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {10939946},\\n\\tdoi = {10.2741/3071},\\n\\tabstract = {Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.},\\n\\tnumber = {13},\\n\\tjournal = {Frontiers in Bioscience},\\n\\tauthor = {Carnicer, R. and Guzman, M.A. and Acin, S. and Surra, J.C. and Navarro, M.A. and Arbones-Mainar, J.M. and Arnal, C. and Morales, R. and Osada, J.},\\n\\tyear = {2008},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Carnicer, R.\",\"Guzman, M.\",\"Acin, S.\",\"Surra, J.\",\"Navarro, M.\",\"Arbones-Mainar, J.\",\"Arnal, C.\",\"Morales, R.\",\"Osada, J.\"],\"key\":\"carnicer_genetic_2008\",\"id\":\"carnicer_genetic_2008\",\"bibbaseid\":\"carnicer-guzman-acin-surra-navarro-arbonesmainar-arnal-morales-etal-geneticbackgroundinapolipoproteinaiandcystathioninesynthasedeficiency-2008\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties\",\"volume\":\"258\",\"copyright\":\"All rights reserved\",\"issn\":\"18727786\",\"doi\":\"10.1016/j.cbi.2016.07.014\",\"abstract\":\"© 2016 Elsevier Ireland Ltd Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release w as measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC 50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone – or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.\",\"journal\":\"Chemico-Biological Interactions\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Les\",\"Parellada\"],\"firstnames\":[\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Deleruyelle\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Cassagnes\"],\"firstnames\":[\"L.-E.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Boutin\"],\"firstnames\":[\"J.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Balogh\"],\"firstnames\":[\"B.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Biron\"],\"firstnames\":[\"S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Marceau\"],\"firstnames\":[\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Richard\"],\"firstnames\":[\"D.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Nepveu\"],\"firstnames\":[\"F.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Mauriège\"],\"firstnames\":[\"P.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Carpéné\"],\"firstnames\":[\"C.\"],\"suffixes\":[]}],\"year\":\"2016\",\"bibtex\":\"@article{les_parellada_piceatannol_2016,\\n\\ttitle = {Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties},\\n\\tvolume = {258},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {18727786},\\n\\tdoi = {10.1016/j.cbi.2016.07.014},\\n\\tabstract = {© 2016 Elsevier Ireland Ltd Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release w as measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC 50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone – or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.},\\n\\tjournal = {Chemico-Biological Interactions},\\n\\tauthor = {Les Parellada, F. and Deleruyelle, S. and Cassagnes, L.-E. and Boutin, J.A. and Balogh, B. and Arbones-Mainar, J.M. and Biron, S. and Marceau, P. and Richard, D. and Nepveu, F. and Mauriège, P. and Carpéné, C.},\\n\\tyear = {2016},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Les Parellada, F.\",\"Deleruyelle, S.\",\"Cassagnes, L.\",\"Boutin, J.\",\"Balogh, B.\",\"Arbones-Mainar, J.\",\"Biron, S.\",\"Marceau, P.\",\"Richard, D.\",\"Nepveu, F.\",\"Mauriège, P.\",\"Carpéné, C.\"],\"key\":\"les_parellada_piceatannol_2016\",\"id\":\"les_parellada_piceatannol_2016\",\"bibbaseid\":\"lesparellada-deleruyelle-cassagnes-boutin-balogh-arbonesmainar-biron-marceau-etal-piceatannolandresveratrolshareinhibitoryeffectsonhydrogenperoxidereleasemonoamineoxidaseandlipogenicactivitiesinadiposetissuebutdifferintheirantilipolyticproperties-2016\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Human LDL receptor enhances sequestration of apoE4 and VLDL remnants on the surface of hepatocytes but not their internalization in mice\",\"volume\":\"28\",\"copyright\":\"All rights reserved\",\"issn\":\"10795642\",\"doi\":\"10.1161/ATVBAHA.108.164863\",\"abstract\":\"Objective - In humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR). Methods and Results-Primary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-density lipoprotein (VLDL) remnants accumulated on the hepatocyte surface in apoE4 mice with high LDLR, but they were internalized poorly. In contrast, apoE2-GFP did not accumulate on the hepatocyte surface even when the LDLR expression was high, but apoE2 mice with high LDLR internalized the remnants avidly without sequestering them on the hepatocyte surface. Conclusions-The high affinity of apoE4 to the LDLR enhances VLDL sequestration on the hepatocyte surface but delays their internalization. This delay likely increases VLDL conversion to cholesterol-enriched remnants in apoE4 mice with high LDLR, and probably to LDL in humans with apoE4. © 2008 American Heart Association, Inc.\",\"number\":\"6\",\"journal\":\"Arteriosclerosis, Thrombosis, and Vascular Biology\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Altenburg\"],\"firstnames\":[\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"L.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Wilder\"],\"firstnames\":[\"J.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"N.\"],\"suffixes\":[]}],\"year\":\"2008\",\"bibtex\":\"@article{altenburg_human_2008,\\n\\ttitle = {Human {LDL} receptor enhances sequestration of {apoE4} and {VLDL} remnants on the surface of hepatocytes but not their internalization in mice},\\n\\tvolume = {28},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {10795642},\\n\\tdoi = {10.1161/ATVBAHA.108.164863},\\n\\tabstract = {Objective - In humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR). Methods and Results-Primary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-density lipoprotein (VLDL) remnants accumulated on the hepatocyte surface in apoE4 mice with high LDLR, but they were internalized poorly. In contrast, apoE2-GFP did not accumulate on the hepatocyte surface even when the LDLR expression was high, but apoE2 mice with high LDLR internalized the remnants avidly without sequestering them on the hepatocyte surface. Conclusions-The high affinity of apoE4 to the LDLR enhances VLDL sequestration on the hepatocyte surface but delays their internalization. This delay likely increases VLDL conversion to cholesterol-enriched remnants in apoE4 mice with high LDLR, and probably to LDL in humans with apoE4. © 2008 American Heart Association, Inc.},\\n\\tnumber = {6},\\n\\tjournal = {Arteriosclerosis, Thrombosis, and Vascular Biology},\\n\\tauthor = {Altenburg, M. and Arbones-Mainar, J. and Johnson, L. and Wilder, J. and Maeda, N.},\\n\\tyear = {2008},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Altenburg, M.\",\"Arbones-Mainar, J.\",\"Johnson, L.\",\"Wilder, J.\",\"Maeda, N.\"],\"key\":\"altenburg_human_2008\",\"id\":\"altenburg_human_2008\",\"bibbaseid\":\"altenburg-arbonesmainar-johnson-wilder-maeda-humanldlreceptorenhancessequestrationofapoe4andvldlremnantsonthesurfaceofhepatocytesbutnottheirinternalizationinmice-2008\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Impaired adipogenic response to thiazolidinediones in mice expressing human apolipoproteinE4\",\"volume\":\"24\",\"copyright\":\"All rights reserved\",\"issn\":\"15306860\",\"doi\":\"10.1096/fj.10-159517\",\"abstract\":\"Thiazolidinediones (TZDs) are insulin sensitizers used to treat patients with insulin resistance. To assess potential gene-drug interactions, mice expressing human apolipoprotein E3 or E4 (APOE3 or APOE4) were fed a Western-type high-fat diet for 12 wk, at which time they developed similarly impaired glucose tolerance. Supplementing the diet with rosiglitazone (1.5 mg/g body weight) for an additional 4 wk improved plasma lipid profiles in both APOE3 and APOE4 mice. However, glucose tolerance improved only in APOE3 mice. Induction of adipogenesis and lipogenesis was severely blunted in adipose tissues, but not in the livers, of APOE4 mice. Consequently, lipids were channeled to the liver, causing marked steatosis in these mice. Impaired glucose tolerance was not a prerequisite for this adverse effect, and long-term treatment with rosiglitazone altered liver enzymes and caused hepatic fibrosis in APOE4 mice. Finally, TZDs failed to stimulate PPARγ activation and adipocyte differentiation in preadipocytes and embryonic fibroblasts isolated from APOE4 mice compared to those from APOE3 mice. We conclude that the effects of TZDs are APOE isoform dependent, and that the metabolic damage observed in APOE4 mice is rooted in an impaired activation of the adipogenic program in the adipose tissues expressing APOE4. © FASEB.\",\"number\":\"10\",\"journal\":\"FASEB Journal\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J.M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"L.A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Altenburg\"],\"firstnames\":[\"M.K.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Kim\"],\"firstnames\":[\"H.-S.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"N.\"],\"suffixes\":[]}],\"year\":\"2010\",\"bibtex\":\"@article{arbones-mainar_impaired_2010,\\n\\ttitle = {Impaired adipogenic response to thiazolidinediones in mice expressing human {apolipoproteinE4}},\\n\\tvolume = {24},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {15306860},\\n\\tdoi = {10.1096/fj.10-159517},\\n\\tabstract = {Thiazolidinediones (TZDs) are insulin sensitizers used to treat patients with insulin resistance. To assess potential gene-drug interactions, mice expressing human apolipoprotein E3 or E4 (APOE3 or APOE4) were fed a Western-type high-fat diet for 12 wk, at which time they developed similarly impaired glucose tolerance. Supplementing the diet with rosiglitazone (1.5 mg/g body weight) for an additional 4 wk improved plasma lipid profiles in both APOE3 and APOE4 mice. However, glucose tolerance improved only in APOE3 mice. Induction of adipogenesis and lipogenesis was severely blunted in adipose tissues, but not in the livers, of APOE4 mice. Consequently, lipids were channeled to the liver, causing marked steatosis in these mice. Impaired glucose tolerance was not a prerequisite for this adverse effect, and long-term treatment with rosiglitazone altered liver enzymes and caused hepatic fibrosis in APOE4 mice. Finally, TZDs failed to stimulate PPARγ activation and adipocyte differentiation in preadipocytes and embryonic fibroblasts isolated from APOE4 mice compared to those from APOE3 mice. We conclude that the effects of TZDs are APOE isoform dependent, and that the metabolic damage observed in APOE4 mice is rooted in an impaired activation of the adipogenic program in the adipose tissues expressing APOE4. © FASEB.},\\n\\tnumber = {10},\\n\\tjournal = {FASEB Journal},\\n\\tauthor = {Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Kim, H.-S. and Maeda, N.},\\n\\tyear = {2010},\\n}\\n\\n\\n\\n\",\"author_short\":[\"Arbones-Mainar, J.\",\"Johnson, L.\",\"Altenburg, M.\",\"Kim, H.\",\"Maeda, N.\"],\"key\":\"arbones-mainar_impaired_2010\",\"id\":\"arbones-mainar_impaired_2010\",\"bibbaseid\":\"arbonesmainar-johnson-altenburg-kim-maeda-impairedadipogenicresponsetothiazolidinedionesinmiceexpressinghumanapolipoproteine4-2010\",\"role\":\"author\",\"urls\":{},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats\",\"volume\":\"72\",\"copyright\":\"All rights reserved\",\"issn\":\"1138-7548\",\"url\":\"http://dx.doi.org/10.1007/s13105-015-0457-1\",\"doi\":\"10.1007/s13105-015-0457-1\",\"language\":\"English\",\"number\":\"3\",\"journal\":\"Journal of Physiology and Biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Llarena\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Andrade\"],\"firstnames\":[\"Fernando\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hasnaoui\"],\"firstnames\":[\"Mounia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Portillo\"],\"firstnames\":[\"MaríaP.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Pérez-Matute\"],\"firstnames\":[\"Patricia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"JoseM.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Hijona\"],\"firstnames\":[\"Elizabeth\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Villanueva-Millán\"],\"firstnames\":[\"MaríaJesús\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aguirre\"],\"firstnames\":[\"Leixuri\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Carpéné\"],\"firstnames\":[\"Christian\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Aldámiz-Echevarría\"],\"firstnames\":[\"Luis\"],\"suffixes\":[]}],\"year\":\"2016\",\"note\":\"Publisher: Springer Netherlands\",\"pages\":\"555–566\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view\",\"bibtex\":\"@article{Llarena2015,\\n\\ttitle = {Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese {Zucker} rats},\\n\\tvolume = {72},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {1138-7548},\\n\\turl = {http://dx.doi.org/10.1007/s13105-015-0457-1},\\n\\tdoi = {10.1007/s13105-015-0457-1},\\n\\tlanguage = {English},\\n\\tnumber = {3},\\n\\tjournal = {Journal of Physiology and Biochemistry},\\n\\tauthor = {Llarena, Marta and Andrade, Fernando and Hasnaoui, Mounia and Portillo, MaríaP. and Pérez-Matute, Patricia and Arbones-Mainar, JoseM. and Hijona, Elizabeth and Villanueva-Millán, MaríaJesús and Aguirre, Leixuri and Carpéné, Christian and Aldámiz-Echevarría, Luis},\\n\\tyear = {2016},\\n\\tnote = {Publisher: Springer Netherlands},\\n\\tpages = {555--566},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Llarena, M.\",\"Andrade, F.\",\"Hasnaoui, M.\",\"Portillo, M.\",\"Pérez-Matute, P.\",\"Arbones-Mainar, J.\",\"Hijona, E.\",\"Villanueva-Millán, M.\",\"Aguirre, L.\",\"Carpéné, C.\",\"Aldámiz-Echevarría, L.\"],\"key\":\"Llarena2015\",\"id\":\"Llarena2015\",\"bibbaseid\":\"llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://dx.doi.org/10.1007/s13105-015-0457-1\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in\",\"copyright\":\"All rights reserved\",\"doi\":\"10.1096/fj.201600859R\",\"journal\":\"FASEB J.\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Martinez-Fernandez\"],\"firstnames\":[\"Leyre\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gonzalez-Muniesa\"],\"firstnames\":[\"Pedro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Laiglesia\"],\"firstnames\":[\"Laura\",\"M\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sainz\"],\"firstnames\":[\"Neira\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Prieto-Hontoria\"],\"firstnames\":[\"Pedro\",\"L\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Escote\"],\"firstnames\":[\"Xavier\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Odriozola\"],\"firstnames\":[\"Leticia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Corrales\"],\"firstnames\":[\"Fernando\",\"J\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martinez\"],\"firstnames\":[\"Jose\",\"A\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Moreno-Aliaga\"],\"firstnames\":[\"Maria\",\"J\"],\"suffixes\":[]}],\"year\":\"2017\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view\",\"bibtex\":\"@article{Mart2017,\\n\\ttitle = {Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in},\\n\\tcopyright = {All rights reserved},\\n\\tdoi = {10.1096/fj.201600859R},\\n\\tjournal = {FASEB J.},\\n\\tauthor = {Martinez-Fernandez, Leyre and Gonzalez-Muniesa, Pedro and Laiglesia, Laura M and Sainz, Neira and Prieto-Hontoria, Pedro L and Escote, Xavier and Odriozola, Leticia and Corrales, Fernando J and Arbones-Mainar, Jose M and Martinez, Jose A and Moreno-Aliaga, Maria J},\\n\\tyear = {2017},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Martinez-Fernandez, L.\",\"Gonzalez-Muniesa, P.\",\"Laiglesia, L. M\",\"Sainz, N.\",\"Prieto-Hontoria, P. L\",\"Escote, X.\",\"Odriozola, L.\",\"Corrales, F. J\",\"Arbones-Mainar, J. M\",\"Martinez, J. A\",\"Moreno-Aliaga, M. J\"],\"key\":\"Mart2017\",\"id\":\"Mart2017\",\"bibbaseid\":\"martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017\",\"role\":\"author\",\"urls\":{\" paper\":\"https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Knock-down of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells.\",\"copyright\":\"All rights reserved\",\"issn\":\"0363-6143\",\"url\":\"http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016\",\"doi\":\"10.1152/ajpcell.00246.2016\",\"number\":\"312\",\"journal\":\"American Journal of Physiology - Cell Physiology\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Perez-Diaz\"],\"firstnames\":[\"Sergio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Rodriguez\"],\"firstnames\":[\"Beatriz\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gonzalez-Irazabal\"],\"firstnames\":[\"Yolanda\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Valero\"],\"firstnames\":[\"Monica\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Lagos-Lizan\"],\"firstnames\":[\"Javier\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"JM\"],\"suffixes\":[]}],\"year\":\"2017\",\"pages\":\"C83–C91\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view\",\"bibtex\":\"@article{Perez-Diaz2016a,\\n\\ttitle = {Knock-down of {PTRF} ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells.},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {0363-6143},\\n\\turl = {http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016},\\n\\tdoi = {10.1152/ajpcell.00246.2016},\\n\\tnumber = {312},\\n\\tjournal = {American Journal of Physiology - Cell Physiology},\\n\\tauthor = {Perez-Diaz, Sergio and Garcia-Rodriguez, Beatriz and Gonzalez-Irazabal, Yolanda and Valero, Monica and Lagos-Lizan, Javier and Arbones-Mainar, JM},\\n\\tyear = {2017},\\n\\tpages = {C83--C91},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Perez-Diaz, S.\",\"Garcia-Rodriguez, B.\",\"Gonzalez-Irazabal, Y.\",\"Valero, M.\",\"Lagos-Lizan, J.\",\"Arbones-Mainar, J.\"],\"key\":\"Perez-Diaz2016a\",\"id\":\"Perez-Diaz2016a\",\"bibbaseid\":\"perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"book\",\"type\":\"book\",\"title\":\"Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4\",\"copyright\":\"All rights reserved\",\"isbn\":\"1476-5497\",\"url\":\"http://dx.doi.org/10.1038/ijo.2016.93\",\"publisher\":\"Macmillan Publishers Limited\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"J\",\"M\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Johnson\"],\"firstnames\":[\"L\",\"A\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Torres-Perez\"],\"firstnames\":[\"E\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia\"],\"firstnames\":[\"A\",\"E\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Perez-Diaz\"],\"firstnames\":[\"S\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Raber\"],\"firstnames\":[\"J\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Maeda\"],\"firstnames\":[\"N\"],\"suffixes\":[]}],\"month\":\"May\",\"year\":\"2016\",\"note\":\"Publication Title: Int J Obes\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view\",\"bibtex\":\"@book{Arbones-Mainar2016,\\n\\ttitle = {Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human {APOE4}},\\n\\tcopyright = {All rights reserved},\\n\\tisbn = {1476-5497},\\n\\turl = {http://dx.doi.org/10.1038/ijo.2016.93},\\n\\tpublisher = {Macmillan Publishers Limited},\\n\\tauthor = {Arbones-Mainar, J M and Johnson, L A and Torres-Perez, E and Garcia, A E and Perez-Diaz, S and Raber, J and Maeda, N},\\n\\tmonth = may,\\n\\tyear = {2016},\\n\\tnote = {Publication Title: Int J Obes},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view}\\n}\\n\\n\\n\\n\\n\\n\\n\\n\",\"author_short\":[\"Arbones-Mainar, J M\",\"Johnson, L A\",\"Torres-Perez, E\",\"Garcia, A E\",\"Perez-Diaz, S\",\"Raber, J\",\"Maeda, N\"],\"key\":\"Arbones-Mainar2016\",\"id\":\"Arbones-Mainar2016\",\"bibbaseid\":\"arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://dx.doi.org/10.1038/ijo.2016.93\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women\",\"volume\":\"105\",\"copyright\":\"All rights reserved\",\"issn\":\"15565653\",\"url\":\"http://dx.doi.org/10.1016/j.fertnstert.2016.02.021\",\"doi\":\"10.1016/j.fertnstert.2016.02.021\",\"abstract\":\"Objective To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. Design Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations. Setting Not applicable. Patient(s) Women without miscarriages (controls) and women who miscarried at least once (cases). Intervention(s) None. Main Outcome Measure(s) A group of women (n = 1,372) successfully followed for 25??years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. Result(s) In white women followed up for 25??years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95% confidence interval, 1.04???2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2% in the APOE*2 carriers compared with 27.8% and 24.8% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06???2.05). Conclusion(s) This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.\",\"number\":\"6\",\"journal\":\"Fertility and Sterility\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Gamundi-Segura\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Torres-Perez\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Sanz-Paris\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"March\",\"year\":\"2016\",\"pmid\":\"26952784\",\"note\":\"Publisher: Elsevier\",\"pages\":\"1554–1560.e1\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view\",\"bibtex\":\"@article{Gamundi-Segura2016,\\n\\ttitle = {Interaction of apolipoprotein {E} gene polymorphisms on miscarriage risk in black and white {American} women},\\n\\tvolume = {105},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {15565653},\\n\\turl = {http://dx.doi.org/10.1016/j.fertnstert.2016.02.021},\\n\\tdoi = {10.1016/j.fertnstert.2016.02.021},\\n\\tabstract = {Objective To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. Design Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations. Setting Not applicable. Patient(s) Women without miscarriages (controls) and women who miscarried at least once (cases). Intervention(s) None. Main Outcome Measure(s) A group of women (n = 1,372) successfully followed for 25??years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. Result(s) In white women followed up for 25??years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95\\\\% confidence interval, 1.04???2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2\\\\% in the APOE*2 carriers compared with 27.8\\\\% and 24.8\\\\% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06???2.05). Conclusion(s) This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.},\\n\\tnumber = {6},\\n\\tjournal = {Fertility and Sterility},\\n\\tauthor = {Gamundi-Segura, Silvia and Torres-Perez, Elena and Sanz-Paris, Alejandro and Arbones-Mainar, Jose M.},\\n\\tmonth = mar,\\n\\tyear = {2016},\\n\\tpmid = {26952784},\\n\\tnote = {Publisher: Elsevier},\\n\\tpages = {1554--1560.e1},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Gamundi-Segura, S.\",\"Torres-Perez, E.\",\"Sanz-Paris, A.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Gamundi-Segura2016\",\"id\":\"Gamundi-Segura2016\",\"bibbaseid\":\"gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://dx.doi.org/10.1016/j.fertnstert.2016.02.021\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro\",\"copyright\":\"All rights reserved\",\"issn\":\"18778755\",\"url\":\"http://www.ncbi.nlm.nih.gov/pubmed/25686566\",\"doi\":\"10.1007/s13105-015-0393-0\",\"abstract\":\"Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.\",\"urldate\":\"2015-02-18\",\"journal\":\"Journal of Physiology and Biochemistry\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Gamundi-Segura\"],\"firstnames\":[\"Silvia\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Serna\"],\"firstnames\":[\"Jose\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Oehninger\"],\"firstnames\":[\"Sergio\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Horcajadas\"],\"firstnames\":[\"Jose\",\"A.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"February\",\"year\":\"2015\",\"pmid\":\"25686566\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view\",\"bibtex\":\"@article{Gamundi-Segura2015,\\n\\ttitle = {Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {18778755},\\n\\turl = {http://www.ncbi.nlm.nih.gov/pubmed/25686566},\\n\\tdoi = {10.1007/s13105-015-0393-0},\\n\\tabstract = {Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.},\\n\\turldate = {2015-02-18},\\n\\tjournal = {Journal of Physiology and Biochemistry},\\n\\tauthor = {Gamundi-Segura, Silvia and Serna, Jose and Oehninger, Sergio and Horcajadas, Jose A. and Arbones-Mainar, Jose M.},\\n\\tmonth = feb,\\n\\tyear = {2015},\\n\\tpmid = {25686566},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Gamundi-Segura, S.\",\"Serna, J.\",\"Oehninger, S.\",\"Horcajadas, J. A.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Gamundi-Segura2015\",\"id\":\"Gamundi-Segura2015\",\"bibbaseid\":\"gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.ncbi.nlm.nih.gov/pubmed/25686566\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Application of the new ESPEN definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study\",\"volume\":\"35\",\"copyright\":\"All rights reserved\",\"issn\":\"02615614\",\"url\":\"http://www.sciencedirect.com/science/article/pii/S0261561416000893\",\"doi\":\"10.1016/j.clnu.2016.02.018\",\"abstract\":\"BACKGROUND & AIMS The European Society for Clinical Nutrition and Metabolism (ESPEN) recently provided new diagnosis criteria of malnutrition and called to confirm those criteria in specific populations⁠⁠. The aims of our study were 1) to determine the prevalence of malnutrition according to the new ESPEN definition in elder hospitalized diabetic patients, and 2) to evaluate whether this new diagnosis of malnutrition predicted clinical outcomes in these patients. METHODS 1014 hospitalized diabetic patients (≥65 years) from 35 hospitals in Spain were screened for being at risk of malnutrition using the short version of the Mini Nutritional Assessment. Subsequently, at risk individuals were considered malnourished if they met at least one of the two options: 1) body mass index (BMI) \\\\textless18.5 kg/m2, or 2) unintentional weight loss \\\\textgreater5% of their body weight with reduced BMI (\\\\textless20 kg/m2 in subjects younger than 70 years or \\\\textless22 kg/m2 in subjects older than 70 years)⁠ RESULTS The new ESPEN definition, with MNA-SF as initial screening, identified 68 malnourished geriatric individuals with diabetes (6.73% of the cohort). Additionally, malnutrition lengthened the hospital stay, increased 2.7 times the odds of dying in hospital, and decreased to one third the odds of being discharged home. CONCLUSIONS Our study confirms that the new ESPEN definition for the diagnosis of malnutrition is a reliable tool that is capable of predicting clinical outcomes in a large population of elder hospitalized individuals with diabetes.\",\"number\":\"6\",\"journal\":\"Clinical Nutrition\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Sanz-París\"],\"firstnames\":[\"Alejandro\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Gómez-Candela\"],\"firstnames\":[\"Carmen\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Martín-Palmero\"],\"firstnames\":[\"Ángela\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"García-Almeida\"],\"firstnames\":[\"José\",\"M.\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Burgos-Pelaez\"],\"firstnames\":[\"Rosa\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Matía-Martin\"],\"firstnames\":[\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"year\":\"2016\",\"pages\":\"1564–1567\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view\",\"bibtex\":\"@article{Sanz-Paris2016,\\n\\ttitle = {Application of the new {ESPEN} definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study},\\n\\tvolume = {35},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {02615614},\\n\\turl = {http://www.sciencedirect.com/science/article/pii/S0261561416000893},\\n\\tdoi = {10.1016/j.clnu.2016.02.018},\\n\\tabstract = {BACKGROUND \\\\& AIMS The European Society for Clinical Nutrition and Metabolism (ESPEN) recently provided new diagnosis criteria of malnutrition and called to confirm those criteria in specific populations⁠⁠. The aims of our study were 1) to determine the prevalence of malnutrition according to the new ESPEN definition in elder hospitalized diabetic patients, and 2) to evaluate whether this new diagnosis of malnutrition predicted clinical outcomes in these patients. METHODS 1014 hospitalized diabetic patients (≥65 years) from 35 hospitals in Spain were screened for being at risk of malnutrition using the short version of the Mini Nutritional Assessment. Subsequently, at risk individuals were considered malnourished if they met at least one of the two options: 1) body mass index (BMI) {\\\\textless}18.5 kg/m2, or 2) unintentional weight loss {\\\\textgreater}5\\\\% of their body weight with reduced BMI ({\\\\textless}20 kg/m2 in subjects younger than 70 years or {\\\\textless}22 kg/m2 in subjects older than 70 years)⁠ RESULTS The new ESPEN definition, with MNA-SF as initial screening, identified 68 malnourished geriatric individuals with diabetes (6.73\\\\% of the cohort). Additionally, malnutrition lengthened the hospital stay, increased 2.7 times the odds of dying in hospital, and decreased to one third the odds of being discharged home. CONCLUSIONS Our study confirms that the new ESPEN definition for the diagnosis of malnutrition is a reliable tool that is capable of predicting clinical outcomes in a large population of elder hospitalized individuals with diabetes.},\\n\\tnumber = {6},\\n\\tjournal = {Clinical Nutrition},\\n\\tauthor = {Sanz-París, Alejandro and Gómez-Candela, Carmen and Martín-Palmero, Ángela and García-Almeida, José M. and Burgos-Pelaez, Rosa and Matía-Martin, Pilar and Arbones-Mainar, Jose M.},\\n\\tyear = {2016},\\n\\tpages = {1564--1567},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view}\\n}\\n\\n\\n\\n\",\"author_short\":[\"Sanz-París, A.\",\"Gómez-Candela, C.\",\"Martín-Palmero, Á.\",\"García-Almeida, J. M.\",\"Burgos-Pelaez, R.\",\"Matía-Martin, P.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Sanz-Paris2016\",\"id\":\"Sanz-Paris2016\",\"bibbaseid\":\"sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.sciencedirect.com/science/article/pii/S0261561416000893\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"},{\"bibtype\":\"article\",\"type\":\"article\",\"title\":\"Apolipoprotein E4 association with metabolic syndrome depends on body fatness\",\"volume\":\"245\",\"copyright\":\"All rights reserved\",\"issn\":\"00219150\",\"url\":\"http://www.sciencedirect.com/science/article/pii/S0021915015302240\",\"doi\":\"10.1016/j.atherosclerosis.2015.11.029\",\"abstract\":\"BACKGROUND AND AIMS The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness. METHODS & RESULTS We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95% CI, 1.07-1.55). CONCLUSIONS Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.\",\"urldate\":\"2015-12-18\",\"journal\":\"Atherosclerosis\",\"author\":[{\"propositions\":[],\"lastnames\":[\"Torres-Perez\"],\"firstnames\":[\"Elena\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Ledesma\"],\"firstnames\":[\"Marta\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Garcia-Sobreviela\"],\"firstnames\":[\"Maria\",\"Pilar\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Leon-Latre\"],\"firstnames\":[\"Montserrat\"],\"suffixes\":[]},{\"propositions\":[],\"lastnames\":[\"Arbones-Mainar\"],\"firstnames\":[\"Jose\",\"M.\"],\"suffixes\":[]}],\"month\":\"February\",\"year\":\"2016\",\"pages\":\"35–42\",\"url_paper\":\"https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view\",\"bibtex\":\"@article{Torres-Perez2016,\\n\\ttitle = {Apolipoprotein {E4} association with metabolic syndrome depends on body fatness},\\n\\tvolume = {245},\\n\\tcopyright = {All rights reserved},\\n\\tissn = {00219150},\\n\\turl = {http://www.sciencedirect.com/science/article/pii/S0021915015302240},\\n\\tdoi = {10.1016/j.atherosclerosis.2015.11.029},\\n\\tabstract = {BACKGROUND AND AIMS The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness. METHODS \\\\& RESULTS We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95\\\\% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95\\\\% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95\\\\% CI, 1.07-1.55). CONCLUSIONS Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.},\\n\\turldate = {2015-12-18},\\n\\tjournal = {Atherosclerosis},\\n\\tauthor = {Torres-Perez, Elena and Ledesma, Marta and Garcia-Sobreviela, Maria Pilar and Leon-Latre, Montserrat and Arbones-Mainar, Jose M.},\\n\\tmonth = feb,\\n\\tyear = {2016},\\n\\tpages = {35--42},\\n\\turl_paper={https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view}\\n}\\n\",\"author_short\":[\"Torres-Perez, E.\",\"Ledesma, M.\",\"Garcia-Sobreviela, M. P.\",\"Leon-Latre, M.\",\"Arbones-Mainar, J. M.\"],\"key\":\"Torres-Perez2016\",\"id\":\"Torres-Perez2016\",\"bibbaseid\":\"torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016\",\"role\":\"author\",\"urls\":{\"Paper\":\"http://www.sciencedirect.com/science/article/pii/S0021915015302240\",\" paper\":\"https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view\"},\"metadata\":{\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\"html\":\"\"}],\n      metadata: {\"owner\":\"arbones-mainar, j\",\"authorlinks\":{\"arbones-mainar, j\":\"http://adipofat.com/pubs-2\"}},\n      ownerID: \"TxZyPC8onLwE29pw5\"\n    };\n  </script>\n\n  <script type=\"text/javascript\">\n  var site$;\n  if (typeof $ != 'undefined') {\n    console.log('existing jquery: storing and then restoring');\n    site$ = $;\n    $ = null;\n  }\n  </script>\n\n  <script src=\"https://ajax.googleapis.com/ajax/libs/jquery/2.2.4/jquery.min.js\">\n  </script>\n  <script type=\"text/javascript\">\n  if (site$) {\n    console.log('existing jquery: avoiding conflict and restoring');\n    bb$ = $.noConflict(true);\n    $ = site$;\n  } else {\n    bb$ = $;\n  }\n  </script>\n\n  <script src=\"//bibbase.org/js/bibbase.min.js\"\n          type=\"text/javascript\">\n  </script>\n\n  <script type=\"text/javascript\"\n          src=\"https://cdnjs.cloudflare.com/ajax/libs/mathjax/2.7.1/MathJax.js?config=TeX-AMS-MML_HTMLorMML\">\n  </script>\n  <script type=\"text/x-mathjax-config\">\n    MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]},\n                        skipTags: [\"body\"],\n                        processClass: \"bibbase_paper\"});\n  </script>\n\n  <style>\n  @media print {\n    .dontprint {\n        display: none !important;\n    }\n\n  .bibbase_group {\n    background-color: #E0E0E0;\n    font-style: italic;\n    font-size: larger;\n    text-shadow: 0px 0px 3px #FFFFFF;\n    border-radius: 4px 4px 4px 4px;\n    -moz-border-radius: 4px 4px 4px 4px;\n    -webkit-border-radius: 4px;\n    padding: 5px 40px 5px;\n    margin-top: 10px;\n    margin-bottom: 5px;\n    cursor: pointer;\n  }\n\n  .bibbase_paper {\n    margin-bottom: 5px;\n  }\n\n  }\n  </style>\n\n  \n  <div style=\"float: right; margin-right: 10px; margin-top: 10px; text-align: right; font-size: 12px\">\n    generated by\n    <a href=\"//bibbase.org\"\n       onclick=\"trackOutboundLink('bibbase', 'logo clicked', window.location.href, '//bibbase.org'); return false;\">\n      <img src=\"//bibbase.org/img/logo.svg\"\n           style=\"vertical-align: middle; margin-left: 3px; height: 16px;\"/\n           alt=\"bibbase.org\"\n           title=\"BibBase – The easiest way to maintain your publications page.\"\n        ></a>\n    \n  </div>\n  \n\n  <div id=\"bibbase_header\" class=\"dontprint\" style=\"\">\n\n    <ul class=\"nav nav-pills\" style=\"margin: 0px;\">\n\n      <li class=\"dropdown\" id=\"groupby_dropdown\">\n      <a class=\"dropdown-toggle\"\n         data-toggle=\"dropdown\"\n         href=\"#\">\n          Group by\n          <b class=\"caret\"></b>\n      </a>\n      <ul class=\"dropdown-menu\">\n        <li class=\"groupby year\"><a onclick=\"groupby('year')\">\n            Year</a>\n        </li>\n        <li class=\"groupby author\"><a onclick=\"groupby('author_short')\">\n            Author</a>\n        </li>\n        <li class=\"groupby type\"><a onclick=\"groupby('type')\">\n            Type</a>\n        </li>\n        <li class=\"groupby keyword\"><a onclick=\"groupby('keyword')\">\n            Keyword</a>\n        </li>\n        <li class=\"groupby downloads\"><a onclick=\"groupby('downloads')\">\n            Downloads</a>\n        </li>\n      </ul>\n      </li>\n\n\n      <li class=\"dropdown\" id=\"menu_dropdown\">\n      <a class=\"dropdown-toggle\"\n         data-toggle=\"dropdown\"\n         href=\"#\" alt=\"controls\">\n          <i class=\"fa fa-reorder\" alt=\"controls\"></i>\n          <b class=\"caret\"></b>\n      </a>\n      <ul class=\"dropdown-menu\">\n        <li>\n          <a onclick=\"toggleAll()\">\n            <i class=\"fa fa-chevron-down fa-fw\"></i> Expand/Collapse All\n          </a>\n        </li>\n        <li>\n          <a download=\"arbones\" href=\"data:text/bibtex;base64,@article{lopez-yus_crispr/cas9-mediated_2023,
	title = {{CRISPR}/{Cas9}-mediated deletion of adipocyte genes associated with {NAFLD} alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro},
	volume = {325},
	copyright = {All rights reserved},
	issn = {0363-6143, 1522-1563},
	url = {https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023},
	doi = {10.1152/ajpcell.00291.2023},
	abstract = {Obesity is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD), and the subcutaneous white adipose tissue (scWAT) is the primary lipid storage depot and regulates lipid ﬂuxes to other organs. Our previous work identiﬁed genes upregulated in scWAT of patients with NAFLD: SOCS3, DUSP1, and SIK1. Herein, we knocked down (KD) their expression in human adipose-derived mesenchymal stem cells (hADMSCs) using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology and characterized their phenotype. We found that SOCS3, DUSP1, and SIK1 expression in hADMSC-derived adipocytes was not critical for adipogenesis. However, the metabolic characterization of the cells suggested that the genes played important roles in lipid metabolism. Reduction of SIK1 expression signiﬁcantly increased both de novo lipogenesis (DNL) and palmitate-induced lipogenesis (PIL). Editing out SOCS3 reduced DNL while increasing isoproterenolinduced lipolysis and insulin-induced palmitate accumulation. Conversely, DUSP1 reduced PIL and DNL. Moreover, RNAsequencing analysis of edited cells showed that these genes not only altered lipid metabolism but also other biological pathways related to inﬂammatory processes, in the case of DUSP1, extracellular matrix remodeling for SOCS3, or cellular transport for SIK1. Finally, to evaluate a possible adipocyte-hepatocyte axis, human hepatoma HepG2 cells were cocultured with edited hADMSCs-derived adipocytes in the presence of [3H]-palmitate. All HepG2 cells cultured with DUSP1-, SIK1-, or SOCS3-KD adipocytes decreased [3H]-palmitate accumulation compared with control adipocytes. These results support our hypotheses that SOCS3, DUSP1, and SIK1 regulate multiple aspects of adipocyte function, which may play a role in the progression of obesityassociated comorbidities, such as NAFLD.},
	language = {en},
	number = {5},
	urldate = {2023-10-31},
	journal = {American Journal of Physiology-Cell Physiology},
	author = {Lopez-Yus, Marta and Frendo-Cumbo, Scott and Del Moral-Bergos, Raquel and Garcia-Sobreviela, Maria Pilar and Bernal-Monterde, Vanesa and Rydén, Mikael and Lorente-Cebrian, Silvia and Arbones-Mainar, Jose M.},
	month = nov,
	year = {2023},
	pages = {C1178--C1189},
	url_paper={https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view}
}





@article{lopez-yus_gene_2023,
	title = {Gene {Therapy} {Based} on {Mesenchymal} {Stem} {Cells} {Derived} from {Adipose} {Tissue} for the {Treatment} of {Obesity} and {Its} {Metabolic} {Complications}},
	volume = {24},
	copyright = {All rights reserved},
	doi = {10.3390/ijms24087468},
	abstract = {Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.},
	number = {8},
	journal = {International Journal of Molecular Sciences},
	author = {Lopez-Yus, Marta and García-Sobreviela, Maria Pilar and del Moral-Bergos, Raquel and Arbones-Mainar, Jose M.},
	month = apr,
	year = {2023},
	note = {Publisher: MDPI},
}





@article{lopez-yus_identification_2022,
	title = {Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression},
	volume = {36},
	copyright = {All rights reserved},
	doi = {10.1096/fj.202200118RR},
	abstract = {Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.},
	number = {8},
	journal = {FASEB Journal},
	author = {Lopez-Yus, Marta and Lorente-Cebrian, Silvia and del Moral-Bergos, Raquel and Hörndler, Carlos and Garcia-Sobreviela, Maria Pilar and Casamayor, Carmen and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},
	month = aug,
	year = {2022},
	note = {Publisher: John Wiley and Sons Inc},
}





@article{laiglesia_maresin_2023,
	title = {Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice},
	volume = {74},
	copyright = {All rights reserved},
	issn = {2212-8778},
	url = {https://www.sciencedirect.com/science/article/pii/S2212877823000832},
	doi = {10.1016/j.molmet.2023.101749},
	abstract = {Objective
Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning.
Methods
MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice.
Results
In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice.
Conclusions
These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.},
	language = {en},
	urldate = {2023-06-22},
	journal = {Molecular Metabolism},
	author = {Laiglesia, Laura M. and Escoté, Xavier and Sáinz, Neira and Felix-Soriano, Elisa and Santamaría, Eva and Collantes, María and Fernández-Galilea, Marta and Colón-Mesa, Ignacio and Martínez-Fernández, Leyre and Quesada-López, Tania and Quesada-Vázquez, Sergio and Rodríguez-Ortigosa, Carlos and Arbones-Mainar, José M. and Valverde, Ángela M. and Martínez, J Alfredo and Dalli, Jesmond and Herrero, Laura and Lorente-Cebrián, Silvia and Villarroya, Francesc and Moreno-Aliaga, María J.},
	month = aug,
	year = {2023},
	pages = {101749},
	url_paper={https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view}
}









@article{casas-deza_triglyceride-rich_2023,
	title = {Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis {C} receiving direct-acting antivirals},
	volume = {375},
	copyright = {All rights reserved},
	issn = {00219150},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867},
	doi = {10.1016/j.atherosclerosis.2023.05.003},
	abstract = {Background \& aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardio­ vascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradi­ cation of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy.
Methods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR).
Results: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (− 22\%) and HDL-TG (− 18\%) after one-year follow-up.
Conclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this asso­ ciation. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evo­ lution of glucose tolerance and IR after HCV eradication.},
	language = {en},
	urldate = {2023-05-31},
	journal = {Atherosclerosis},
	author = {Casas-Deza, Diego and Espina, Silvia and Martínez-Sapiña, Ana and Del Moral-Bergos, Raquel and Garcia-Sobreviela, Maria Pilar and Lopez-Yus, Marta and Calmarza, Pilar and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},
	month = jun,
	year = {2023},
	pages = {59--66},
	url_paper={https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view}
}









@article{casas-deza_evaluation_2022,
	title = {Evaluation of {Cardiovascular} {Risk} {Factors} after {Hepatitis} {C} {Virus} {Eradication} with {Direct}-{Acting} {Antivirals} in a {Cohort} of {Treatment}-{Naïve} {Patients} without {History} of {Cardiovascular} {Disease}},
	volume = {11},
	copyright = {http://creativecommons.org/licenses/by/3.0/},
	issn = {2077-0383},
	url = {https://www.mdpi.com/2077-0383/11/14/4049},
	doi = {10.3390/jcm11144049},
	abstract = {Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53\% female, 9.6\% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4\% of patients, requiring initiation of statins in 15\%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.},
	language = {en},
	number = {14},
	urldate = {2022-12-15},
	journal = {Journal of Clinical Medicine},
	author = {Casas-Deza, Diego and Martínez-Sapiña, Ana and Espina, Silvia and Garcia-Rodriguez, Beatriz and Fernandez-Bonilla, Eva M. and Sanz-Paris, Alejandro and Gonzalez-Irazabal, Yolanda and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},
	month = jan,
	year = {2022},
	note = {Number: 14
Publisher: Multidisciplinary Digital Publishing Institute},
	pages = {4049},
	url_paper={https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view}
}









@article{espina_role_2022,
	title = {Role of {Branched}-{Chain} {Amino} {Acids} and {Their} {Derivative} β-{Hydroxy}-β-{Methylbutyrate} in {Liver} {Cirrhosis}},
	volume = {11},
	copyright = {http://creativecommons.org/licenses/by/3.0/},
	issn = {2077-0383},
	url = {https://www.mdpi.com/2077-0383/11/24/7337},
	doi = {10.3390/jcm11247337},
	abstract = {Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.},
	language = {en},
	number = {24},
	urldate = {2022-12-13},
	journal = {Journal of Clinical Medicine},
	author = {Espina, Silvia and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Casas-Deza, Diego and Arbonés-Mainar, Jose Miguel},
	month = jan,
	year = {2022},
	note = {Number: 24
Publisher: Multidisciplinary Digital Publishing Institute},
	pages = {7337},
	url_paper={https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view}
}









@article{casas-deza_effectiveness_2022,
	title = {Effectiveness and {Safety} of {Ustekinumab} in {Elderly} {Patients} with {Crohn}’s {Disease}: {Real} {World} {Evidence} {From} the {ENEIDA} {Registry}},
	copyright = {All rights reserved},
	issn = {1873-9946, 1876-4479},
	shorttitle = {Effectiveness and {Safety} of {Ustekinumab} in {Elderly} {Patients} with {Crohn}’s {Disease}},
	url = {https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892},
	doi = {10.1093/ecco-jcc/jjac108},
	abstract = {Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD.
Methods: Elderly patients [{\textgreater}60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54.
Results: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4\%, p = 0.20], 32 [53.0\% vs 54.5\%, p = 0.26] and 54 [57.8\% vs 51.1\%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2\% vs 11.2\%, p = 0.350], including severe infections [7.1\% vs 7.3\%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7\% vs 4.3\%, p = 0.003].
Conclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.},
	language = {en},
	urldate = {2022-09-29},
	journal = {Journal of Crohn's and Colitis},
	author = {Casas-Deza, Diego and Lamuela-Calvo, Luis Javier and Gomollón, Fernando and Arbonés-Mainar, José Miguel and Caballol, Berta and Gisbert, Javier P and Rivero, Montserrat and Sánchez-Rodríguez, Eugenia and Arias García, Lara and Gutiérrez Casbas, Ana and Merino, Olga and Márquez, Lucía and Laredo, Viviana and Martín-Arranz, María Dolores and López Serrano, Pilar and Riestra Menéndez, Sabino and González-Muñoza, Carlos and de Castro Parga, Luisa and Calvo Moya, Marta and Fuentes-Valenzuela, Esteban and Esteve, Maria and Iborra, Marisa and Dura Gil, Miguel and Barreiro-De Acosta, Manuel and Lorente-Poyatos, Rufo Humberto and Manceñido, Noemí and Calafat, Margalida and Rodríguez-Lago, Iago and Guardiola Capo, Jordi and Payeras, Maria Antonia and Morales Alvarado, Víctor Jair and Tardillo, Carlos and Bujanda, Luis and Muñoz-Nuñez, José Fernando and Ber Nieto, Yolanda and Bermejo, Fernando and Almela, Pedro and Navarro-Llavat, Mercè and Martínez Montiel, Pilar and Rodríguez Gutiérrez, Cristina and Van Domselaar, Manuel and Sesé, Eva and Martínez Pérez, Teresa and Ricart, Elena and Chaparro, María and García, María José and López-Sanromán, Antonio and Sicilia, Beatriz and Orts, Beatriz and López-García, Alicia and Martín-Arranz, Eduardo and Pérez-Calle, José Lázaro and de Francisco, Ruth and García-Planella, Esther and Domènech, Eugeni and García-López, y Santiago},
	month = aug,
	year = {2022},
	pages = {jjac108},
	url_paper={https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view}
}





@article{pendse_apolipoprotein_2009,
	title = {Apolipoprotein {E} knock-out and knock-in mice: {Atherosclerosis}, metabolic syndrome, and beyond},
	volume = {50},
	copyright = {All rights reserved},
	issn = {00222275},
	doi = {10.1194/jlr.R800070-JLR200},
	abstract = {Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to studymultiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases. Copyright ©2009 by the American Society for Biochemistry and Molecular Biology, Inc.},
	number = {SUPPL.},
	journal = {Journal of Lipid Research},
	author = {Pendse, A.A. and Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Maeda, N.},
	year = {2009},
}





























































































@article{lopez-yus_identification_2022,
	title = {Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression},
	volume = {36},
	copyright = {All rights reserved},
	issn = {0892-6638},
	url = {https://doi.org/10.1096/fj.202200118RR},
	doi = {https://doi.org/10.1096/fj.202200118RR},
	abstract = {Abstract Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.},
	number = {8},
	journal = {The FASEB Journal},
	author = {Lopez-Yus, Marta and Lorente-Cebrian, Silvia and del Moral-Bergos, Raquel and Hörndler, Carlos and Garcia-Sobreviela, Maria Pilar and Casamayor, Carmen and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M},
	month = aug,
	year = {2022},
	note = {Publisher: John Wiley \& Sons, Ltd},
	pages = {e22429},
	url_paper={https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view}
}









@article{lopez-yus_adiponectin_2021,
	title = {Adiponectin overexpression in {C2C12} myocytes increases lipid oxidation and myofiber transition},
	copyright = {All rights reserved},
	issn = {18778755},
	url = {https://doi.org/10.1007/s13105-021-00836-7},
	doi = {10.1007/s13105-021-00836-7},
	abstract = {Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.},
	number = {0123456789},
	journal = {Journal of Physiology and Biochemistry},
	author = {Lopez-Yus, Marta and Lopez-Perez, Rebeca and Garcia-Sobreviela, Maria Pilar and del Moral-Bergos, Raquel and Lorente-Cebrian, Silvia and Arbones-Mainar, Jose M.},
	year = {2021},
	note = {Publisher: Springer Netherlands
ISBN: 0123456789},
	url_paper={https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view}
}





@article{Carpene2018,
	title = {The {Dietary} {Antioxidant} {Piceatannol} {Inhibits} {Adipogenesis} of {Human} {Adipose} {Mesenchymal} {Stem} {Cells} and {Limits} {Glucose} {Transport} and {Lipogenic} {Activities} in {Adipocytes}},
	volume = {19},
	copyright = {All rights reserved},
	issn = {1422-0067},
	url = {http://www.mdpi.com/1422-0067/19/7/2081},
	doi = {10.3390/ijms19072081},
	abstract = {Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty μM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.},
	number = {7},
	journal = {International Journal of Molecular Sciences},
	author = {Carpéné, Christian and Pejenaute, Héctor and del Moral, Raquel and Boulet, Nathalie and Hijona, Elizabeth and Andrade, Fernando and Villanueva-Millán, J Maria and Aguirre, Leixuri and Arbones-Mainar, José Miguel and Villanueva-Millán, Maria and Aguirre, Leixuri and Arbones-Mainar, José Miguel},
	year = {2018},
	note = {ISBN: 1422-0067},
	pages = {2081},
}





@article{Bernal-Monterde2020,
	title = {{SARS}-{CoV}-2 {Infection} {Induces} a {Dual} {Response} in {Liver} {Function} {Tests}: {Association} with {Mortality} during {Hospitalization}},
	volume = {8},
	copyright = {All rights reserved},
	url = {https://www.mdpi.com/2227-9059/8/9/328},
	doi = {10.3390/biomedicines8090328},
	abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5\%) were discharged (109 (20.5\%) died). A total of 319 (64.3\%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9\%) and GGT (47.3\%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.},
	number = {9},
	journal = {Biomedicines},
	author = {Bernal-Monterde, Vanesa and Casas-Deza, Diego and Letona-Giménez, Laura and de la Llama-Celis, Natalia and Calmarza, Pilar and Sierra-Gabarda, Olivia and Betoré-Glaria, Elena and Martínez-de Lagos, María and Martínez-Barredo, Lucía and Espinosa-Pérez, María and M. Arbones-Mainar, Jose},
	year = {2020},
	note = {ISBN: 2227-9059},
	pages = {328},
	url_paper={https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view}
}





@article{Jariod-Ferrer2019,
	title = {Are {Comorbidities} {Associated} {With} {Overall} {Survival} in {Patients} {With} {Oral} {Squamous} {Cell} {Carcinoma}?},
	volume = {77},
	copyright = {All rights reserved},
	issn = {15315053},
	doi = {10.1016/j.joms.2019.03.007},
	abstract = {Purpose: Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods: A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results: Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion: These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC.},
	number = {9},
	journal = {Journal of Oral and Maxillofacial Surgery},
	author = {Jariod-Ferrer, Úrsula M. and Arbones-Mainar, Jose M. and Gavin-Clavero, Marina A. and Simón-Sanz, M. Victoria and Moral-Saez, Ignacio and Cisneros-Gimeno, Ana I. and Martinez-Trufero, Javier},
	year = {2019},
	pages = {1906--1914},
	url_paper={https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view}
}





@article{Gil-Iturbe2019,
	title = {{GLUT12} and adipose tissue: {Expression}, regulation and its relation with obesity in mice},
	copyright = {All rights reserved},
	issn = {17481716},
	doi = {10.1111/apha.13283},
	abstract = {AIM The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. METHODS Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. RESULTS GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. CONCLUSION We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.},
	number = {April},
	journal = {Acta Physiologica},
	author = {Gil-Iturbe, Eva and Arbones-Mainar, José Miguel and Moreno-Aliaga, María J. and Lostao, María Pilar},
	year = {2019},
	pages = {1--14},
}





@article{Serrano-Oliver2019,
	title = {Neck circumference is associated with nutritional status in elderly nursing home residents},
	volume = {62},
	copyright = {All rights reserved},
	issn = {08999007},
	doi = {10.1016/j.nut.2019.01.015},
	journal = {Nutrition},
	author = {Serrano-Oliver, Antonio and Torres-Anoro, Elena and Lardiés-Sanchez, Beatriz and Arbones-Mainar, Jose M. and Sanz-Paris, Alejandro and Perez-Nogueras, Javier},
	year = {2019},
	pages = {153--157},
	url_paper={https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view}
}





@article{Leroux2019,
	title = {Effects of the amino acid derivatives , β -hydroxy- β -methylbutyrate , taurine , and {N}-methyltyramine , on triacylglycerol breakdown in fat cells},
	copyright = {All rights reserved},
	journal = {Journal of Physiology and Biochemistry},
	author = {Leroux, Mélanie and Lemery, Tristan and Boulet, Nathalie and Briot, Anaïs and Zakaroff, Alexia and Bouloumié, Anne and Andrade, Fernando and Pérez-matute, Patricia and Arbones-mainar, Jose M and Carpéné, Christian},
	year = {2019},
	note = {Publisher: Journal of Physiology and Biochemistry},
	url_paper={https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view}
}





@article{Perez-Diaz2018,
	title = {{PTRF} acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition},
	copyright = {All rights reserved},
	issn = {1138-7548},
	url = {http://link.springer.com/10.1007/s13105-018-0638-9},
	doi = {10.1007/s13105-018-0638-9},
	journal = {Journal of Physiology and Biochemistry},
	author = {Perez-Diaz, Sergio and Garcia-Sobreviela, Maria P. and Gonzalez-Irazabal, Yolanda and Garcia-Rodriguez, Beatriz and Espina, Silvia and Arenaz, Izaskun and Arbones-Mainar, Jose M.},
	year = {2018},
	url_paper={https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view}
}





@article{Martinez-Fernandez2020,
	title = {Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice},
	copyright = {All rights reserved},
	issn = {18778755},
	doi = {10.1007/s13105-020-00775-9},
	abstract = {Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling.},
	journal = {Journal of Physiology and Biochemistry},
	author = {Martínez-Fernández, L. and González-Muniesa, P. and Sáinz, N. and Escoté, X. and Martínez, J. A. and Arbones-Mainar, J. M. and Moreno-Aliaga, M. J.},
	year = {2020},
	note = {Publisher: Journal of Physiology and Biochemistry},
	url_paper={https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view}
}





@article{Sanz-Paris2017,
	title = {Post-lunch triglyceridaemia associates with {HDLc} and insulin resistance in fasting normotriglyceridaemic menopausal women},
	copyright = {All rights reserved},
	issn = {1365277X},
	abstract = {© 2017 The British Dietetic Association Ltd. Objectives: Post-prandial hypertriglyceridaemia (P-HTG) is associated with cardiovascular disease. This association is of paramount importance during menopause, which is also related to reduced high-density lipoprotein-cholesterol (HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at fasting and adhered to a Mediterranean-style eating pattern. Methods: We performed oral fat loading tests (OFLT) in combination with self-measurements of diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women. TG levels {\textgreater} 220 mg dL -1 at any given time during the OFLT served as diagnostic criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to classify these women as having P-HTG according to the OFLT. Insulin resistance was defined as the upper tertile of the homeostatic model assessment of insulin resistance. Results: We found that, despite having normal fasting TG levels, P-HTG was highly prevalent (approximately 40\%). Moreover, self-assessed 3-h post-lunch TG levels {\textgreater} 165 mg dL -1 increased the odds of having hypo-HDL cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women adhering to a Mediterranean eating pattern having their highest energy intake at lunch. Conclusions: Self-assessed 3-h post-lunch TG can be used to study post-prandial TG metabolism in Southern European menopausal women who are normotriglyceridaemic at fasting. Characterising an individual's post-prandial response may help menopausal women to evaluate their risk of cardiovascular disease.},
	journal = {Journal of Human Nutrition and Dietetics},
	author = {Sanz-Paris, A. and Rodriguez-Valle, A. and Navarro, M. A. and Puzo-Foncillas, J. and Arbones-Mainar, J. M.},
	year = {2017},
	doi = {10.1111/jhn.12476},
	note = {Volume: 30
Issue: 6},
	pages = {700--708},
}





@article{Sanz-Paris2020,
	title = {Prevalence of {Malnutrition} and 1-{Year} {All}-{Cause} {Mortality} in {Institutionalized} {Elderly} {Patients} {Comparing} {Different} {Combinations} of the {GLIM} {Criteria}},
	copyright = {All rights reserved},
	issn = {19412444},
	doi = {10.1002/jpen.2029},
	abstract = {Background: The Global Leadership Initiative on Malnutrition (GLIM) provided a new approach for the diagnosis of malnutrition based on a number of phenotypic and etiologic criteria. However, different diagnostic criteria could potentially lead to heterogeneity in the diagnosis. We identified different subsets of criteria to define malnutrition in a cohort of elder nursing-home residents and investigated their clinical utility in terms of 1-year survival. Methods: Our study included all residents (n = 485) from 3 nursing homes. We proposed 12 GLIM models based on different phenotypic and etiologic criteria. The main outcome was 1-year all-cause mortality. We also assessed the sensitivity and specificity for different phenotypic criteria using time-dependent receiver operating characteristic curves, and cutoff values were calculated. Results: During 1 year of follow-ups, 94 deaths occurred. The prevalence of malnutrition was 13.5\% for models based on reduced food intake (RFI) and 10.45\% for models based on inflammation associated with acute disease (IAD). Unadjusted Cox regression analyses showed that malnutrition was associated with a 2.31- to 4.64-fold increase in mortality when diagnosed using IAD-dependent models or with a 1.37- to 1.78-fold increase in mortality using RFI-dependent models. Cutoffs associated with mortality for the phenotypic criteria were lower than those recommended in the GLIM criteria. Conclusion: This study describes the association of several variations of the GLIM model with 1-year mortality in nursing-home residents. However, our data suggest a high heterogeneity to fulfill the GLIM criteria and the necessity of finding specific, tailored cutoff points for the studied populations.},
	journal = {Journal of Parenteral and Enteral Nutrition},
	author = {Sanz-Paris, Alejandro and González Fernández, Mikel and Perez-Nogueras, Javier and Serrano-Oliver, Antonio and Torres-Anoro, Elena and Sanz-Arque, Alejandro and Arbones-Mainar, Jose M.},
	year = {2020},
	pmid = {33043987},
	url_paper={https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view}
}





@article{Hijona2016a,
	title = {Limited beneficial effects of piceatannol supplementation on obesity complications in the obese {Zucker} rat: gut microbiota, metabolic, endocrine, and cardiac aspects},
	copyright = {All rights reserved},
	issn = {1138-7548},
	url = {http://link.springer.com/10.1007/s13105-015-0464-2},
	doi = {10.1007/s13105-015-0464-2},
	number = {72},
	journal = {Journal of physiology and biochemistry},
	author = {Hijona, E. and Aguirre, L. and Pérez-Matute, P. and Villanueva-Millán, M. J. and Mosqueda-Solis, A. and Hasnaoui, M. and Nepveu, F. and Senard, J. M. and Bujanda, L. and Aldámiz-Echevarría, L. and Llarena, M. and Andrade, F. and Perio, P. and Leboulanger, F. and Hijona, L. and Arbones-Mainar, J. M. and Portillo, M.P. and Carpéné, C.},
	year = {2016},
	note = {Publisher: Springer Netherlands},
	pages = {567--582},
	url_paper={https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view}
}





@article{Perez-Diaz2014b,
	title = {Polymerase {I} and transcript release factor ({PTRF}) regulates adipocyte differentiation and determines adipose tissue expandability.},
	volume = {28},
	copyright = {All rights reserved},
	issn = {1530-6860},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24812087},
	doi = {10.1096/fj.14-251165},
	abstract = {Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management.-Perez-Diaz, S., Johnson, L. A., DeKroon, R. M., Moreno-Navarrete, J. M., Alzate, O., Fernandez-Real, J. M., Maeda, N., Arbones-Mainar, J. M. Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.},
	urldate = {2014-05-15},
	journal = {FASEB journal},
	author = {Perez-Diaz, Sergio and Johnson, Lance A. and DeKroon, Robert M. and Moreno-Navarrete, Jose M. and Alzate, Oscar and Fernandez-Real, Jose M. and Maeda, Nobuyo and Arbones-Mainar, Jose M.},
	month = may,
	year = {2014},
	pmid = {24812087},
	pages = {1--11},
	url_paper={https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view}
}





@article{Munoz-Cabrejas2020,
	title = {{ALTERACIONES} {DEL} {METABOLISMO} {LIPÍDICO} {PRODUCIDAS} {POR} {EL} {VIRUS} {DE} {LA} {HEPATITIS} {C} {EN} {PACIENTES} {CON} {INFECCIÓN} {CRÓNICA}},
	volume = {94},
	copyright = {All rights reserved},
	journal = {Rev Esp Salud Pública},
	author = {Muñoz-Cabrejas, Ainara and Espina-Cadena, Silvia and Arbones-Mainar, José Miguel and Moreno-Franco, Belén},
	year = {2020},
	pages = {e1--15},
	url_paper={https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view}
}





@article{Martinez-Martinez2020,
	title = {Beyond the {CNS}: {The} many peripheral roles of {APOE}.},
	volume = {138},
	copyright = {All rights reserved},
	issn = {1095-953X},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/32087284},
	doi = {10.1016/j.nbd.2020.104809},
	abstract = {Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75\% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.},
	number = {November 2019},
	journal = {Neurobiology of disease},
	author = {Martinez-Martínez, Ana B and Torres-Perez, Elena and Devanney, Nicholas and Del Moral, Raquel and Johnson, Lance A and Arbones-Mainar, Jose M},
	year = {2020},
	pmid = {32087284},
	note = {Publisher: Elsevier},
	pages = {104809},
	url_paper={https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view}
}





@article{Johnson2011,
	title = {Apolipoprotein {E4} {Exaggerates} {Diabetic} {Dyslipidemia} and {Atherosclerosis} in {Mice} {Lacking} the {LDL} {Receptor}.},
	volume = {60},
	copyright = {All rights reserved},
	issn = {1939-327X},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&tool=pmcentrez&rendertype=abstract},
	doi = {10.2337/db11-0466},
	abstract = {OBJECTIVE We investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia-a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR(-/-)). RESULTS Diabetic E3LDLR(-/-) and E4LDLR(-/-) mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR(-/-) mice twice as much as in E3LDLR(-/-) mice. Diabetic E4LDLR(-/-) mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR(-/-) mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR(-/-) mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR(-/-) primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR(-/-) hepatocytes concomitant with a 60\% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR(-/-) mice was accompanied by a dramatic increase in atherosclerosis. CONCLUSIONS ApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.},
	number = {9},
	urldate = {2011-09-13},
	journal = {Diabetes},
	author = {Johnson, Lance A and Arbones-Mainar, Jose M and Fox, Raymond G and Pendse, Avani A and Altenburg, Michael K and Kim, Hyung-Suk and Maeda, Nobuyo},
	month = sep,
	year = {2011},
	pmid = {21810592},
	pages = {2285--94},
}





@article{arbones-mainar_differential_2008,
	title = {Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein {E3} and {E4} in mice},
	volume = {32},
	copyright = {All rights reserved},
	issn = {03070565},
	doi = {10.1038/ijo.2008.143},
	abstract = {Objective: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly expressed in adipose tissues. Studies have shown that human APOE*4 is associated with a lower body mass index but with a greater risk of coronary heart disease compared with other APOE alleles. To define the isoform-specific role of apoE in regulating the expandability and functionality of adipose tissues, we investigated the effects of diet-induced obesity in mice whose endogenous Apoe gene has been replaced by either the human APOE*3 or APOE*4 allele. Results: After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed impaired tolerance to glucose and fat overload compared with APOE3 mice. Subcutaneous fat tissues in APOE4 and APOE3 mice after high fat feeding were not different. In contrast, although epididymal fat tissues in APOE4 mice gained 30\% less weight during the high fat feeding than in APOE3 mice, they showed impaired insulin-stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were larger in size than APOE3 adipocytes, and expressed reduced levels of mRNA for peroxisome proliferator-activated receptor γ2 and adiponectin, important markers of adipocyte functionality. Adenoviral expression of apoE3 in apoE-null culture adipocytes induced adiponectin mRNA in a dose-dependent manner, but the induction was significantly blunted in cells overexpressing apoE4. However, in contrast to the apoE3-expressing cells, Glut1, but not Glut4, expression levels were positively correlated with increased apoE4 mRNA, suggesting that apoE4 expression in adipocyte interferes in insulin-sensing pathways. Conclusion: Dysfunctional epididymal adipose tissues contribute to the accelerated impairment of glucose tolerance in APOE4 mice fed a Western-type diet. Our results underscore the importance of functionality of individual fat depots rather than total fat mass as a determinant for metabolic disturbance during diet-induced obesity. © 2008 Macmillan Publishers Limited All rights reserved.},
	number = {10},
	journal = {International Journal of Obesity},
	author = {Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Maeda, N.},
	year = {2008},
}





@article{sarria_understanding_2006,
	title = {Understanding the role of dietary components on atherosclerosis using genetic engineered mouse models},
	volume = {11},
	copyright = {All rights reserved},
	issn = {10939946},
	doi = {10.2741/1852},
	abstract = {The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoicing potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.},
	number = {1 P.889-1198},
	journal = {Frontiers in Bioscience},
	author = {Sarria, A.J. and Surra, J.C. and Acin, S. and Carnicer, R. and Navarro, M.A. and Arbones-Mainar, J.M. and Guillen, N. and Martinez-Gracia, M.V. and Arnal, C. and Osada, J.},
	year = {2006},
}





@article{carnicer_folic_2007,
	title = {Folic acid supplementation delays atherosclerotic lesion development in {apoE}-deficient mice},
	volume = {19},
	copyright = {All rights reserved},
	issn = {15781879},
	doi = {10.1016/S0214-9168(07)74181-5},
	number = {2},
	journal = {Clinica e Investigacion en Arteriosclerosis},
	author = {Carnicer, R. and Navarro, M. and Arbones-Mainar, J.M. and Acin, S. and Guzman, M.A. and Surra, J.C. and Arnal, C. and De Las Heras, M. and Blanco-Vaca, F. and Osada, J. and Antonia Vilaseca, M.},
	year = {2007},
}





@article{Torres-Perez2015,
	title = {The {FAT} expandability ({FATe}) {Project}: {Biomarkers} to determine the limit of expansion and the complications of obesity},
	volume = {14},
	copyright = {All rights reserved},
	issn = {1475-2840},
	url = {http://www.cardiab.com/content/14/1/40},
	doi = {10.1186/s12933-015-0203-6},
	abstract = {BACKGROUND:Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.METHODS/DESIGN:FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance.DISCUSSION:The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.},
	number = {1},
	journal = {Cardiovascular Diabetology},
	author = {Torres-Perez, Elena and Valero, Monica and Garcia-Rodriguez, Beatriz and Gonzalez-Irazabal, Yolanda and Calmarza, Pilar and Calvo-Ruata, Luisa and Ortega, Carmen and Garcia-Sobreviela, Maria and Sanz-Paris, Alejandro and Artigas, Jose and Lagos, Javier and Arbones-Mainar, Jose},
	year = {2015},
	pages = {40},
}





@article{arbones-mainar_extra_2007,
	title = {Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in {APOE}$^{\textrm{-/-}}$mice},
	volume = {6},
	copyright = {All rights reserved},
	issn = {15353893},
	doi = {10.1021/pr070321a},
	abstract = {We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe -/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p  {\textless}  0.05), though Picual olive oil significantly decreased plasma triglycerides (p  {\textless}  0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our "systems biology" approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti-atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis. © 2007 American Chemical Society.},
	number = {10},
	journal = {Journal of Proteome Research},
	author = {Arbones-Mainar, J.M. and Ross, K. and Rucklidge, G.J. and Reid, M. and Duncan, G. and Arthur, J.R. and Horgan, G.W. and Navarro, M.A. and Carnicer, R. and Arnal, C. and Osada, J. and De Roos, B.},
	year = {2007},
}





@article{Llobet2017,
	title = {Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome},
	volume = {13},
	copyright = {All rights reserved},
	issn = {22132317},
	doi = {10.1016/j.redox.2017.05.026},
	abstract = {© 2017 The Authors The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.},
	journal = {Redox Biology},
	author = {Llobet, L. and Bayona-Bafaluy, M.P. and Pacheu-Grau, D. and Torres-Pérez, E. and Arbones-Mainar, J.M. and Navarro, M.Á. and Gómez-Díaz, C. and Montoya, J. and López-Gallardo, E. and Ruiz-Pesini, E.},
	year = {2017},
}





@article{de_roos_divergent_2005,
	title = {Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein {E} knockout mice: {A} proteomics approach},
	volume = {19},
	copyright = {All rights reserved},
	issn = {08926638},
	doi = {10.1096/fj.05-3953fje},
	number = {12},
	journal = {FASEB Journal},
	author = {De Roos, B. and Rucklidge, G. and Reid, M. and Ross, K. and Duncan, G. and Navarro, M.A. and Arbones-Mainar, J.M. and Guzman-Garcia, M.A. and Osada, J. and Browne, J. and Loscher, C.E. and Roche, H.M.},
	year = {2005},
}





@article{Tejedor2014,
	title = {The {Apolipoprotein} {E} {Polymorphism} rs7412 {Associates} with {Body} {Fatness} {Independently} of {Plasma} {Lipids} in {Middle} {Aged} {Men}.},
	volume = {9},
	copyright = {All rights reserved},
	issn = {1932-6203},
	url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&tool=pmcentrez&rendertype=abstract},
	doi = {10.1371/journal.pone.0108605},
	abstract = {BACKGROUND: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.

METHODS: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.

RESULTS: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI{\textgreater}30) for individuals carrying the APOε2 allele, present in 14\% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95\% CI: 1.01-1.59).

CONCLUSIONS: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.},
	number = {9},
	urldate = {2014-11-11},
	journal = {PloS one},
	author = {Tejedor, M Teresa and Garcia-Sobreviela, Maria Pilar and Ledesma, Marta and Arbones-Mainar, Jose M},
	month = jan,
	year = {2014},
	pmid = {25268647},
	pages = {e108605},
}





@book{de_roos_effects_2010,
	title = {The {Effects} of {Olive} {Oils} on {Hepatic} {Lipid} {Metabolism} and {Antioxidant} {Defense} {Mechanisms}: {Insights} from {Proteomics} {Studies}},
	copyright = {All rights reserved},
	isbn = {978-0-12-374420-3},
	abstract = {Olive oil is a natural juice of the olive fruit, and it is a major fat source in the Mediterranean diet. Although this diet is associated with a lower rate of coronary heart disease (CHD), as well as a reduction in all-cause mortality, data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. The Mediterranean diet might protect against coronary heart disease through improvement of the lipoprotein profile, improvement of the postprandial pro-thrombotic profile, lowering of blood pressure, and an improvement in insulin sensitivity both in healthy and in type 2 diabetic patients. These potential beneficial effects of olive oil suggest that its consumption affects hepatic lipid and glucose metabolism. Effects of olive oil on health may be due to both its high content of mono-unsaturated fatty acids or alternatively, due to its polar, minor components, which are rich in antioxidant phenolics. As natural dietary antioxidants, these phenolic compounds may protect the organism against damage caused by oxidant agents like active oxygen species and free radicals. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved.},
	author = {De Roos, B. and Arbones-Mainar, J.M. and Gutiérrez, G.R.},
	year = {2010},
	doi = {10.1016/B978-0-12-374420-3.00095-4},
	note = {Publication Title: Olives and Olive Oil in Health and Disease Prevention},
}





@article{carnicer_genetic_2008,
	title = {Genetic background in apolipoprotein {A}-{I} and cystathionine β-synthase deficiency},
	volume = {13},
	copyright = {All rights reserved},
	issn = {10939946},
	doi = {10.2741/3071},
	abstract = {Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.},
	number = {13},
	journal = {Frontiers in Bioscience},
	author = {Carnicer, R. and Guzman, M.A. and Acin, S. and Surra, J.C. and Navarro, M.A. and Arbones-Mainar, J.M. and Arnal, C. and Morales, R. and Osada, J.},
	year = {2008},
}





@article{les_parellada_piceatannol_2016,
	title = {Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties},
	volume = {258},
	copyright = {All rights reserved},
	issn = {18727786},
	doi = {10.1016/j.cbi.2016.07.014},
	abstract = {© 2016 Elsevier Ireland Ltd Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release w as measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC 50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone – or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.},
	journal = {Chemico-Biological Interactions},
	author = {Les Parellada, F. and Deleruyelle, S. and Cassagnes, L.-E. and Boutin, J.A. and Balogh, B. and Arbones-Mainar, J.M. and Biron, S. and Marceau, P. and Richard, D. and Nepveu, F. and Mauriège, P. and Carpéné, C.},
	year = {2016},
}





@article{altenburg_human_2008,
	title = {Human {LDL} receptor enhances sequestration of {apoE4} and {VLDL} remnants on the surface of hepatocytes but not their internalization in mice},
	volume = {28},
	copyright = {All rights reserved},
	issn = {10795642},
	doi = {10.1161/ATVBAHA.108.164863},
	abstract = {Objective - In humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR). Methods and Results-Primary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-density lipoprotein (VLDL) remnants accumulated on the hepatocyte surface in apoE4 mice with high LDLR, but they were internalized poorly. In contrast, apoE2-GFP did not accumulate on the hepatocyte surface even when the LDLR expression was high, but apoE2 mice with high LDLR internalized the remnants avidly without sequestering them on the hepatocyte surface. Conclusions-The high affinity of apoE4 to the LDLR enhances VLDL sequestration on the hepatocyte surface but delays their internalization. This delay likely increases VLDL conversion to cholesterol-enriched remnants in apoE4 mice with high LDLR, and probably to LDL in humans with apoE4. © 2008 American Heart Association, Inc.},
	number = {6},
	journal = {Arteriosclerosis, Thrombosis, and Vascular Biology},
	author = {Altenburg, M. and Arbones-Mainar, J. and Johnson, L. and Wilder, J. and Maeda, N.},
	year = {2008},
}





@article{arbones-mainar_impaired_2010,
	title = {Impaired adipogenic response to thiazolidinediones in mice expressing human {apolipoproteinE4}},
	volume = {24},
	copyright = {All rights reserved},
	issn = {15306860},
	doi = {10.1096/fj.10-159517},
	abstract = {Thiazolidinediones (TZDs) are insulin sensitizers used to treat patients with insulin resistance. To assess potential gene-drug interactions, mice expressing human apolipoprotein E3 or E4 (APOE3 or APOE4) were fed a Western-type high-fat diet for 12 wk, at which time they developed similarly impaired glucose tolerance. Supplementing the diet with rosiglitazone (1.5 mg/g body weight) for an additional 4 wk improved plasma lipid profiles in both APOE3 and APOE4 mice. However, glucose tolerance improved only in APOE3 mice. Induction of adipogenesis and lipogenesis was severely blunted in adipose tissues, but not in the livers, of APOE4 mice. Consequently, lipids were channeled to the liver, causing marked steatosis in these mice. Impaired glucose tolerance was not a prerequisite for this adverse effect, and long-term treatment with rosiglitazone altered liver enzymes and caused hepatic fibrosis in APOE4 mice. Finally, TZDs failed to stimulate PPARγ activation and adipocyte differentiation in preadipocytes and embryonic fibroblasts isolated from APOE4 mice compared to those from APOE3 mice. We conclude that the effects of TZDs are APOE isoform dependent, and that the metabolic damage observed in APOE4 mice is rooted in an impaired activation of the adipogenic program in the adipose tissues expressing APOE4. © FASEB.},
	number = {10},
	journal = {FASEB Journal},
	author = {Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Kim, H.-S. and Maeda, N.},
	year = {2010},
}





@article{Llarena2015,
	title = {Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese {Zucker} rats},
	volume = {72},
	copyright = {All rights reserved},
	issn = {1138-7548},
	url = {http://dx.doi.org/10.1007/s13105-015-0457-1},
	doi = {10.1007/s13105-015-0457-1},
	language = {English},
	number = {3},
	journal = {Journal of Physiology and Biochemistry},
	author = {Llarena, Marta and Andrade, Fernando and Hasnaoui, Mounia and Portillo, MaríaP. and Pérez-Matute, Patricia and Arbones-Mainar, JoseM. and Hijona, Elizabeth and Villanueva-Millán, MaríaJesús and Aguirre, Leixuri and Carpéné, Christian and Aldámiz-Echevarría, Luis},
	year = {2016},
	note = {Publisher: Springer Netherlands},
	pages = {555--566},
	url_paper={https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view}
}





@article{Mart2017,
	title = {Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in},
	copyright = {All rights reserved},
	doi = {10.1096/fj.201600859R},
	journal = {FASEB J.},
	author = {Martinez-Fernandez, Leyre and Gonzalez-Muniesa, Pedro and Laiglesia, Laura M and Sainz, Neira and Prieto-Hontoria, Pedro L and Escote, Xavier and Odriozola, Leticia and Corrales, Fernando J and Arbones-Mainar, Jose M and Martinez, Jose A and Moreno-Aliaga, Maria J},
	year = {2017},
	url_paper={https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view}
}





@article{Perez-Diaz2016a,
	title = {Knock-down of {PTRF} ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells.},
	copyright = {All rights reserved},
	issn = {0363-6143},
	url = {http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016},
	doi = {10.1152/ajpcell.00246.2016},
	number = {312},
	journal = {American Journal of Physiology - Cell Physiology},
	author = {Perez-Diaz, Sergio and Garcia-Rodriguez, Beatriz and Gonzalez-Irazabal, Yolanda and Valero, Monica and Lagos-Lizan, Javier and Arbones-Mainar, JM},
	year = {2017},
	pages = {C83--C91},
	url_paper={https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view}
}





@book{Arbones-Mainar2016,
	title = {Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human {APOE4}},
	copyright = {All rights reserved},
	isbn = {1476-5497},
	url = {http://dx.doi.org/10.1038/ijo.2016.93},
	publisher = {Macmillan Publishers Limited},
	author = {Arbones-Mainar, J M and Johnson, L A and Torres-Perez, E and Garcia, A E and Perez-Diaz, S and Raber, J and Maeda, N},
	month = may,
	year = {2016},
	note = {Publication Title: Int J Obes},
	url_paper={https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view}
}









@article{Gamundi-Segura2016,
	title = {Interaction of apolipoprotein {E} gene polymorphisms on miscarriage risk in black and white {American} women},
	volume = {105},
	copyright = {All rights reserved},
	issn = {15565653},
	url = {http://dx.doi.org/10.1016/j.fertnstert.2016.02.021},
	doi = {10.1016/j.fertnstert.2016.02.021},
	abstract = {Objective To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. Design Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations. Setting Not applicable. Patient(s) Women without miscarriages (controls) and women who miscarried at least once (cases). Intervention(s) None. Main Outcome Measure(s) A group of women (n = 1,372) successfully followed for 25??years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. Result(s) In white women followed up for 25??years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95\% confidence interval, 1.04???2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2\% in the APOE*2 carriers compared with 27.8\% and 24.8\% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06???2.05). Conclusion(s) This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.},
	number = {6},
	journal = {Fertility and Sterility},
	author = {Gamundi-Segura, Silvia and Torres-Perez, Elena and Sanz-Paris, Alejandro and Arbones-Mainar, Jose M.},
	month = mar,
	year = {2016},
	pmid = {26952784},
	note = {Publisher: Elsevier},
	pages = {1554--1560.e1},
	url_paper={https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view}
}





@article{Gamundi-Segura2015,
	title = {Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro},
	copyright = {All rights reserved},
	issn = {18778755},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/25686566},
	doi = {10.1007/s13105-015-0393-0},
	abstract = {Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.},
	urldate = {2015-02-18},
	journal = {Journal of Physiology and Biochemistry},
	author = {Gamundi-Segura, Silvia and Serna, Jose and Oehninger, Sergio and Horcajadas, Jose A. and Arbones-Mainar, Jose M.},
	month = feb,
	year = {2015},
	pmid = {25686566},
	url_paper={https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view}
}





@article{Sanz-Paris2016,
	title = {Application of the new {ESPEN} definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study},
	volume = {35},
	copyright = {All rights reserved},
	issn = {02615614},
	url = {http://www.sciencedirect.com/science/article/pii/S0261561416000893},
	doi = {10.1016/j.clnu.2016.02.018},
	abstract = {BACKGROUND \& AIMS The European Society for Clinical Nutrition and Metabolism (ESPEN) recently provided new diagnosis criteria of malnutrition and called to confirm those criteria in specific populations⁠⁠. The aims of our study were 1) to determine the prevalence of malnutrition according to the new ESPEN definition in elder hospitalized diabetic patients, and 2) to evaluate whether this new diagnosis of malnutrition predicted clinical outcomes in these patients. METHODS 1014 hospitalized diabetic patients (≥65 years) from 35 hospitals in Spain were screened for being at risk of malnutrition using the short version of the Mini Nutritional Assessment. Subsequently, at risk individuals were considered malnourished if they met at least one of the two options: 1) body mass index (BMI) {\textless}18.5 kg/m2, or 2) unintentional weight loss {\textgreater}5\% of their body weight with reduced BMI ({\textless}20 kg/m2 in subjects younger than 70 years or {\textless}22 kg/m2 in subjects older than 70 years)⁠ RESULTS The new ESPEN definition, with MNA-SF as initial screening, identified 68 malnourished geriatric individuals with diabetes (6.73\% of the cohort). Additionally, malnutrition lengthened the hospital stay, increased 2.7 times the odds of dying in hospital, and decreased to one third the odds of being discharged home. CONCLUSIONS Our study confirms that the new ESPEN definition for the diagnosis of malnutrition is a reliable tool that is capable of predicting clinical outcomes in a large population of elder hospitalized individuals with diabetes.},
	number = {6},
	journal = {Clinical Nutrition},
	author = {Sanz-París, Alejandro and Gómez-Candela, Carmen and Martín-Palmero, Ángela and García-Almeida, José M. and Burgos-Pelaez, Rosa and Matía-Martin, Pilar and Arbones-Mainar, Jose M.},
	year = {2016},
	pages = {1564--1567},
	url_paper={https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view}
}





@article{Torres-Perez2016,
	title = {Apolipoprotein {E4} association with metabolic syndrome depends on body fatness},
	volume = {245},
	copyright = {All rights reserved},
	issn = {00219150},
	url = {http://www.sciencedirect.com/science/article/pii/S0021915015302240},
	doi = {10.1016/j.atherosclerosis.2015.11.029},
	abstract = {BACKGROUND AND AIMS The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness. METHODS \& RESULTS We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95\% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95\% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95\% CI, 1.07-1.55). CONCLUSIONS Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.},
	urldate = {2015-12-18},
	journal = {Atherosclerosis},
	author = {Torres-Perez, Elena and Ledesma, Marta and Garcia-Sobreviela, Maria Pilar and Leon-Latre, Montserrat and Arbones-Mainar, Jose M.},
	month = feb,
	year = {2016},
	pages = {35--42},
	url_paper={https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view}
}
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In order to keep using Mendeley with BibBase past April\n        14th, you need to:\n        <ol>\n          <li>renew the authorization for BibBase on Mendeley, and</li>\n          <li>update the BibBase URL\n            in your page the same way you did when you initially set up\n            this page.\n          </li>\n        </ol>\n      </p>\n\n      <p>\n        <a href=\"http://bibbase.org/cgi-bin/mendeley2/get.py\">\n          <i class=\"fa fa-angle-double-right\"></i>\n          Fix it now</a>\n      </p>\n    </div>\n\n  </div>\n\n\n  <div id=\"bibbase_body\">\n    \n  \n  <div class=\"bibbase_group_whole\" id=\"group_2023\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2023')\"\n      onkeypress=\"toggleGroup('group_2023')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2023</span>\n      <span class=\"bibbase_group_count\">\n        \n        (4)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023', 'https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023', event);\">\n    CRISPR/Cas9-mediated deletion of adipocyte genes associated with NAFLD alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Lopez-Yus, M.; Frendo-Cumbo, S.; Del Moral-Bergos, R.; Garcia-Sobreviela, M. P.; Bernal-Monterde, V.; Rydén, M.; Lorente-Cebrian, S.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>American Journal of Physiology-Cell Physiology</i>, 325(5): C1178–C1189. November 2023.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023\"\n     onclick=\"log_download('lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023', 'https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"CRISPR/Cas9-mediated deletion of adipocyte genes associated with NAFLD alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view\"\n     onclick=\"log_download('lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023', 'https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"CRISPR/Cas9-mediated deletion of adipocyte genes associated with NAFLD alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1152/ajpcell.00291.2023\"\n     onclick=\"log_download('lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023', 'http://doi.org/10.1152/ajpcell.00291.2023', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lopezyus-frendocumbo-delmoralbergos-garciasobreviela-bernalmonterde-rydn-lorentecebrian-arbonesmainar-crisprcas9mediateddeletionofadipocytegenesassociatedwithnafldaltersadipocytelipidhandlingandreducessteatosisinhepatocytesinvitro-2023')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{lopez-yus_crispr/cas9-mediated_2023,\n\ttitle = {{CRISPR}/{Cas9}-mediated deletion of adipocyte genes associated with {NAFLD} alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro},\n\tvolume = {325},\n\tcopyright = {All rights reserved},\n\tissn = {0363-6143, 1522-1563},\n\turl = {https://journals.physiology.org/doi/10.1152/ajpcell.00291.2023},\n\tdoi = {10.1152/ajpcell.00291.2023},\n\tabstract = {Obesity is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD), and the subcutaneous white adipose tissue (scWAT) is the primary lipid storage depot and regulates lipid fluxes to other organs. Our previous work identified genes upregulated in scWAT of patients with NAFLD: SOCS3, DUSP1, and SIK1. Herein, we knocked down (KD) their expression in human adipose-derived mesenchymal stem cells (hADMSCs) using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology and characterized their phenotype. We found that SOCS3, DUSP1, and SIK1 expression in hADMSC-derived adipocytes was not critical for adipogenesis. However, the metabolic characterization of the cells suggested that the genes played important roles in lipid metabolism. Reduction of SIK1 expression significantly increased both de novo lipogenesis (DNL) and palmitate-induced lipogenesis (PIL). Editing out SOCS3 reduced DNL while increasing isoproterenolinduced lipolysis and insulin-induced palmitate accumulation. Conversely, DUSP1 reduced PIL and DNL. Moreover, RNAsequencing analysis of edited cells showed that these genes not only altered lipid metabolism but also other biological pathways related to inflammatory processes, in the case of DUSP1, extracellular matrix remodeling for SOCS3, or cellular transport for SIK1. Finally, to evaluate a possible adipocyte-hepatocyte axis, human hepatoma HepG2 cells were cocultured with edited hADMSCs-derived adipocytes in the presence of [3H]-palmitate. All HepG2 cells cultured with DUSP1-, SIK1-, or SOCS3-KD adipocytes decreased [3H]-palmitate accumulation compared with control adipocytes. These results support our hypotheses that SOCS3, DUSP1, and SIK1 regulate multiple aspects of adipocyte function, which may play a role in the progression of obesityassociated comorbidities, such as NAFLD.},\n\tlanguage = {en},\n\tnumber = {5},\n\turldate = {2023-10-31},\n\tjournal = {American Journal of Physiology-Cell Physiology},\n\tauthor = {Lopez-Yus, Marta and Frendo-Cumbo, Scott and Del Moral-Bergos, Raquel and Garcia-Sobreviela, Maria Pilar and Bernal-Monterde, Vanesa and Rydén, Mikael and Lorente-Cebrian, Silvia and Arbones-Mainar, Jose M.},\n\tmonth = nov,\n\tyear = {2023},\n\tpages = {C1178--C1189},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/SEQMQCME/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Obesity is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD), and the subcutaneous white adipose tissue (scWAT) is the primary lipid storage depot and regulates lipid fluxes to other organs. Our previous work identified genes upregulated in scWAT of patients with NAFLD: SOCS3, DUSP1, and SIK1. Herein, we knocked down (KD) their expression in human adipose-derived mesenchymal stem cells (hADMSCs) using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology and characterized their phenotype. We found that SOCS3, DUSP1, and SIK1 expression in hADMSC-derived adipocytes was not critical for adipogenesis. However, the metabolic characterization of the cells suggested that the genes played important roles in lipid metabolism. Reduction of SIK1 expression significantly increased both de novo lipogenesis (DNL) and palmitate-induced lipogenesis (PIL). Editing out SOCS3 reduced DNL while increasing isoproterenolinduced lipolysis and insulin-induced palmitate accumulation. Conversely, DUSP1 reduced PIL and DNL. Moreover, RNAsequencing analysis of edited cells showed that these genes not only altered lipid metabolism but also other biological pathways related to inflammatory processes, in the case of DUSP1, extracellular matrix remodeling for SOCS3, or cellular transport for SIK1. Finally, to evaluate a possible adipocyte-hepatocyte axis, human hepatoma HepG2 cells were cocultured with edited hADMSCs-derived adipocytes in the presence of [3H]-palmitate. All HepG2 cells cultured with DUSP1-, SIK1-, or SOCS3-KD adipocytes decreased [3H]-palmitate accumulation compared with control adipocytes. These results support our hypotheses that SOCS3, DUSP1, and SIK1 regulate multiple aspects of adipocyte function, which may play a role in the progression of obesityassociated comorbidities, such as NAFLD.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"lopezyus-garcasobreviela-delmoralbergos-arbonesmainar-genetherapybasedonmesenchymalstemcellsderivedfromadiposetissueforthetreatmentofobesityanditsmetaboliccomplications-2023\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Lopez-Yus, M.; García-Sobreviela, M. P.; del Moral-Bergos, R.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>International Journal of Molecular Sciences</i>, 24(8). April 2023.\n  <span class=\"note\">Publisher: MDPI</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.3390/ijms24087468\"\n     onclick=\"log_download('lopezyus-garcasobreviela-delmoralbergos-arbonesmainar-genetherapybasedonmesenchymalstemcellsderivedfromadiposetissueforthetreatmentofobesityanditsmetaboliccomplications-2023', 'http://doi.org/10.3390/ijms24087468', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lopezyus-garcasobreviela-delmoralbergos-arbonesmainar-genetherapybasedonmesenchymalstemcellsderivedfromadiposetissueforthetreatmentofobesityanditsmetaboliccomplications-2023\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lopezyus-garcasobreviela-delmoralbergos-arbonesmainar-genetherapybasedonmesenchymalstemcellsderivedfromadiposetissueforthetreatmentofobesityanditsmetaboliccomplications-2023')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{lopez-yus_gene_2023,\n\ttitle = {Gene {Therapy} {Based} on {Mesenchymal} {Stem} {Cells} {Derived} from {Adipose} {Tissue} for the {Treatment} of {Obesity} and {Its} {Metabolic} {Complications}},\n\tvolume = {24},\n\tcopyright = {All rights reserved},\n\tdoi = {10.3390/ijms24087468},\n\tabstract = {Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.},\n\tnumber = {8},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Lopez-Yus, Marta and García-Sobreviela, Maria Pilar and del Moral-Bergos, Raquel and Arbones-Mainar, Jose M.},\n\tmonth = apr,\n\tyear = {2023},\n\tnote = {Publisher: MDPI},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.sciencedirect.com/science/article/pii/S2212877823000832\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023', 'https://www.sciencedirect.com/science/article/pii/S2212877823000832', event);\">\n    Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Laiglesia, L. M.; Escoté, X.; Sáinz, N.; Felix-Soriano, E.; Santamaría, E.; Collantes, M.; Fernández-Galilea, M.; Colón-Mesa, I.; Martínez-Fernández, L.; Quesada-López, T.; Quesada-Vázquez, S.; Rodríguez-Ortigosa, C.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>; Valverde, Á. M.; Martínez, J A.; Dalli, J.; Herrero, L.; Lorente-Cebrián, S.; Villarroya, F.;  and Moreno-Aliaga, M. J.\n</span>\n\n  \n\n</span>\n\n  <i>Molecular Metabolism</i>, 74: 101749. August 2023.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.sciencedirect.com/science/article/pii/S2212877823000832\"\n     onclick=\"log_download('laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023', 'https://www.sciencedirect.com/science/article/pii/S2212877823000832', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view\"\n     onclick=\"log_download('laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023', 'https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.molmet.2023.101749\"\n     onclick=\"log_download('laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023', 'http://doi.org/10.1016/j.molmet.2023.101749', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('laiglesia-escot-sinz-felixsoriano-santamara-collantes-fernndezgalilea-colnmesa-etal-maresin1activatesbrownadiposetissueandpromotesbrowningofwhiteadiposetissueinmice-2023')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{laiglesia_maresin_2023,\n\ttitle = {Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice},\n\tvolume = {74},\n\tcopyright = {All rights reserved},\n\tissn = {2212-8778},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2212877823000832},\n\tdoi = {10.1016/j.molmet.2023.101749},\n\tabstract = {Objective\nMaresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning.\nMethods\nMaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice.\nResults\nIn cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice.\nConclusions\nThese data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.},\n\tlanguage = {en},\n\turldate = {2023-06-22},\n\tjournal = {Molecular Metabolism},\n\tauthor = {Laiglesia, Laura M. and Escoté, Xavier and Sáinz, Neira and Felix-Soriano, Elisa and Santamaría, Eva and Collantes, María and Fernández-Galilea, Marta and Colón-Mesa, Ignacio and Martínez-Fernández, Leyre and Quesada-López, Tania and Quesada-Vázquez, Sergio and Rodríguez-Ortigosa, Carlos and Arbones-Mainar, José M. and Valverde, Ángela M. and Martínez, J Alfredo and Dalli, Jesmond and Herrero, Laura and Lorente-Cebrián, Silvia and Villarroya, Francesc and Moreno-Aliaga, María J.},\n\tmonth = aug,\n\tyear = {2023},\n\tpages = {101749},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/KS4VQJKI/file/view}\n}\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Objective Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. Methods MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice. Results In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice. Conclusions These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023', 'https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867', event);\">\n    Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Casas-Deza, D.; Espina, S.; Martínez-Sapiña, A.; Del Moral-Bergos, R.; Garcia-Sobreviela, M. P.; Lopez-Yus, M.; Calmarza, P.; Bernal-Monterde, V.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Atherosclerosis</i>, 375: 59–66. June 2023.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867\"\n     onclick=\"log_download('casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023', 'https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view\"\n     onclick=\"log_download('casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023', 'https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.atherosclerosis.2023.05.003\"\n     onclick=\"log_download('casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023', 'http://doi.org/10.1016/j.atherosclerosis.2023.05.003', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('casasdeza-espina-martnezsapia-delmoralbergos-garciasobreviela-lopezyus-calmarza-bernalmonterde-etal-triglyceriderichlipoproteinsandinsulinresistanceinpatientswithchronichepatitiscreceivingdirectactingantivirals-2023')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{casas-deza_triglyceride-rich_2023,\n\ttitle = {Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis {C} receiving direct-acting antivirals},\n\tvolume = {375},\n\tcopyright = {All rights reserved},\n\tissn = {00219150},\n\turl = {https://linkinghub.elsevier.com/retrieve/pii/S0021915023001867},\n\tdoi = {10.1016/j.atherosclerosis.2023.05.003},\n\tabstract = {Background \\&amp; aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardio­ vascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradi­ cation of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy.\nMethods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR).\nResults: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (− 22\\%) and HDL-TG (− 18\\%) after one-year follow-up.\nConclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this asso­ ciation. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evo­ lution of glucose tolerance and IR after HCV eradication.},\n\tlanguage = {en},\n\turldate = {2023-05-31},\n\tjournal = {Atherosclerosis},\n\tauthor = {Casas-Deza, Diego and Espina, Silvia and Martínez-Sapiña, Ana and Del Moral-Bergos, Raquel and Garcia-Sobreviela, Maria Pilar and Lopez-Yus, Marta and Calmarza, Pilar and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},\n\tmonth = jun,\n\tyear = {2023},\n\tpages = {59--66},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/B5CZQFAI/file/view}\n}\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Background & aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardio­ vascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradi­ cation of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy. Methods: We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR). Results: FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (− 22%) and HDL-TG (− 18%) after one-year follow-up. Conclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this asso­ ciation. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evo­ lution of glucose tolerance and IR after HCV eradication.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2022\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2022')\"\n      onkeypress=\"toggleGroup('group_2022')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2022</span>\n      <span class=\"bibbase_group_count\">\n        \n        (5)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Lopez-Yus, M.; Lorente-Cebrian, S.; del Moral-Bergos, R.; Hörndler, C.; Garcia-Sobreviela, M. P.; Casamayor, C.; Sanz-Paris, A.; Bernal-Monterde, V.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>FASEB Journal</i>, 36(8). August 2022.\n  <span class=\"note\">Publisher: John Wiley and Sons Inc</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1096/fj.202200118RR\"\n     onclick=\"log_download('lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022', 'http://doi.org/10.1096/fj.202200118RR', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{lopez-yus_identification_2022,\n\ttitle = {Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression},\n\tvolume = {36},\n\tcopyright = {All rights reserved},\n\tdoi = {10.1096/fj.202200118RR},\n\tabstract = {Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.},\n\tnumber = {8},\n\tjournal = {FASEB Journal},\n\tauthor = {Lopez-Yus, Marta and Lorente-Cebrian, Silvia and del Moral-Bergos, Raquel and Hörndler, Carlos and Garcia-Sobreviela, Maria Pilar and Casamayor, Carmen and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},\n\tmonth = aug,\n\tyear = {2022},\n\tnote = {Publisher: John Wiley and Sons Inc},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.mdpi.com/2077-0383/11/14/4049\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022', 'https://www.mdpi.com/2077-0383/11/14/4049', event);\">\n    Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Casas-Deza, D.; Martínez-Sapiña, A.; Espina, S.; Garcia-Rodriguez, B.; Fernandez-Bonilla, E. M.; Sanz-Paris, A.; Gonzalez-Irazabal, Y.; Bernal-Monterde, V.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Clinical Medicine</i>, 11(14): 4049. January 2022.\n  <span class=\"note\">Number: 14 Publisher: Multidisciplinary Digital Publishing Institute</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.mdpi.com/2077-0383/11/14/4049\"\n     onclick=\"log_download('casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022', 'https://www.mdpi.com/2077-0383/11/14/4049', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view\"\n     onclick=\"log_download('casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022', 'https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3390/jcm11144049\"\n     onclick=\"log_download('casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022', 'http://doi.org/10.3390/jcm11144049', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('casasdeza-martnezsapia-espina-garciarodriguez-fernandezbonilla-sanzparis-gonzalezirazabal-bernalmonterde-etal-evaluationofcardiovascularriskfactorsafterhepatitiscviruseradicationwithdirectactingantiviralsinacohortoftreatmentnavepatientswithouthistoryofcardiovasculardisease-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{casas-deza_evaluation_2022,\n\ttitle = {Evaluation of {Cardiovascular} {Risk} {Factors} after {Hepatitis} {C} {Virus} {Eradication} with {Direct}-{Acting} {Antivirals} in a {Cohort} of {Treatment}-{Naïve} {Patients} without {History} of {Cardiovascular} {Disease}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2077-0383},\n\turl = {https://www.mdpi.com/2077-0383/11/14/4049},\n\tdoi = {10.3390/jcm11144049},\n\tabstract = {Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53\\% female, 9.6\\% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4\\% of patients, requiring initiation of statins in 15\\%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.},\n\tlanguage = {en},\n\tnumber = {14},\n\turldate = {2022-12-15},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {Casas-Deza, Diego and Martínez-Sapiña, Ana and Espina, Silvia and Garcia-Rodriguez, Beatriz and Fernandez-Bonilla, Eva M. and Sanz-Paris, Alejandro and Gonzalez-Irazabal, Yolanda and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M.},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Number: 14\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tpages = {4049},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/T7F3JJ9J/file/view}\n}\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.mdpi.com/2077-0383/11/24/7337\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022', 'https://www.mdpi.com/2077-0383/11/24/7337', event);\">\n    Role of Branched-Chain Amino Acids and Their Derivative β-Hydroxy-β-Methylbutyrate in Liver Cirrhosis.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Espina, S.; Sanz-Paris, A.; Bernal-Monterde, V.; Casas-Deza, D.;  and Arbonés-Mainar, J. M.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Clinical Medicine</i>, 11(24): 7337. January 2022.\n  <span class=\"note\">Number: 24 Publisher: Multidisciplinary Digital Publishing Institute</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.mdpi.com/2077-0383/11/24/7337\"\n     onclick=\"log_download('espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022', 'https://www.mdpi.com/2077-0383/11/24/7337', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Role of Branched-Chain Amino Acids and Their Derivative β-Hydroxy-β-Methylbutyrate in Liver Cirrhosis [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view\"\n     onclick=\"log_download('espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022', 'https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Role of Branched-Chain Amino Acids and Their Derivative β-Hydroxy-β-Methylbutyrate in Liver Cirrhosis [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3390/jcm11247337\"\n     onclick=\"log_download('espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022', 'http://doi.org/10.3390/jcm11247337', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('espina-sanzparis-bernalmonterde-casasdeza-arbonsmainar-roleofbranchedchainaminoacidsandtheirderivativehydroxymethylbutyrateinlivercirrhosis-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{espina_role_2022,\n\ttitle = {Role of {Branched}-{Chain} {Amino} {Acids} and {Their} {Derivative} β-{Hydroxy}-β-{Methylbutyrate} in {Liver} {Cirrhosis}},\n\tvolume = {11},\n\tcopyright = {http://creativecommons.org/licenses/by/3.0/},\n\tissn = {2077-0383},\n\turl = {https://www.mdpi.com/2077-0383/11/24/7337},\n\tdoi = {10.3390/jcm11247337},\n\tabstract = {Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.},\n\tlanguage = {en},\n\tnumber = {24},\n\turldate = {2022-12-13},\n\tjournal = {Journal of Clinical Medicine},\n\tauthor = {Espina, Silvia and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Casas-Deza, Diego and Arbonés-Mainar, Jose Miguel},\n\tmonth = jan,\n\tyear = {2022},\n\tnote = {Number: 24\nPublisher: Multidisciplinary Digital Publishing Institute},\n\tpages = {7337},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/Q6YTT58F/file/view}\n}\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative β-hydroxy-β-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022', 'https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892', event);\">\n    Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn’s Disease: Real World Evidence From the ENEIDA Registry.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Casas-Deza, D.; Lamuela-Calvo, L. J.; Gomollón, F.; Arbonés-Mainar, J. M.; Caballol, B.; Gisbert, J. P; Rivero, M.; Sánchez-Rodríguez, E.; Arias García, L.; Gutiérrez Casbas, A.; Merino, O.; Márquez, L.; Laredo, V.; Martín-Arranz, M. D.; López Serrano, P.; Riestra Menéndez, S.; González-Muñoza, C.; de Castro Parga, L.; Calvo Moya, M.; Fuentes-Valenzuela, E.; Esteve, M.; Iborra, M.; Dura Gil, M.; Barreiro-De Acosta, M.; Lorente-Poyatos, R. H.; Manceñido, N.; Calafat, M.; Rodríguez-Lago, I.; Guardiola Capo, J.; Payeras, M. A.; Morales Alvarado, V. J.; Tardillo, C.; Bujanda, L.; Muñoz-Nuñez, J. F.; Ber Nieto, Y.; Bermejo, F.; Almela, P.; Navarro-Llavat, M.; Martínez Montiel, P.; Rodríguez Gutiérrez, C.; Van Domselaar, M.; Sesé, E.; Martínez Pérez, T.; Ricart, E.; Chaparro, M.; García, M. J.; López-Sanromán, A.; Sicilia, B.; Orts, B.; López-García, A.; Martín-Arranz, E.; Pérez-Calle, J. L.; de Francisco, R.; García-Planella, E.; Domènech, E.;  and García-López, y S.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Crohn's and Colitis</i>,jjac108. August 2022.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892\"\n     onclick=\"log_download('casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022', 'https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn’s Disease: Real World Evidence From the ENEIDA Registry [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view\"\n     onclick=\"log_download('casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022', 'https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn’s Disease: Real World Evidence From the ENEIDA Registry [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1093/ecco-jcc/jjac108\"\n     onclick=\"log_download('casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022', 'http://doi.org/10.1093/ecco-jcc/jjac108', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n  &nbsp;\n  <span class=\"bibbase_stats_paper\" style=\"color: #777;\">\n    <span>1 download</span>\n  </span>\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('casasdeza-lamuelacalvo-gomolln-arbonsmainar-caballol-gisbert-rivero-snchezrodrguez-etal-effectivenessandsafetyofustekinumabinelderlypatientswithcrohnsdiseaserealworldevidencefromtheeneidaregistry-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{casas-deza_effectiveness_2022,\n\ttitle = {Effectiveness and {Safety} of {Ustekinumab} in {Elderly} {Patients} with {Crohn}’s {Disease}: {Real} {World} {Evidence} {From} the {ENEIDA} {Registry}},\n\tcopyright = {All rights reserved},\n\tissn = {1873-9946, 1876-4479},\n\tshorttitle = {Effectiveness and {Safety} of {Ustekinumab} in {Elderly} {Patients} with {Crohn}’s {Disease}},\n\turl = {https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjac108/6652892},\n\tdoi = {10.1093/ecco-jcc/jjac108},\n\tabstract = {Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD.\nMethods: Elderly patients [{\\textgreater}60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54.\nResults: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4\\%, p = 0.20], 32 [53.0\\% vs 54.5\\%, p = 0.26] and 54 [57.8\\% vs 51.1\\%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2\\% vs 11.2\\%, p = 0.350], including severe infections [7.1\\% vs 7.3\\%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7\\% vs 4.3\\%, p = 0.003].\nConclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.},\n\tlanguage = {en},\n\turldate = {2022-09-29},\n\tjournal = {Journal of Crohn&#x27;s and Colitis},\n\tauthor = {Casas-Deza, Diego and Lamuela-Calvo, Luis Javier and Gomollón, Fernando and Arbonés-Mainar, José Miguel and Caballol, Berta and Gisbert, Javier P and Rivero, Montserrat and Sánchez-Rodríguez, Eugenia and Arias García, Lara and Gutiérrez Casbas, Ana and Merino, Olga and Márquez, Lucía and Laredo, Viviana and Martín-Arranz, María Dolores and López Serrano, Pilar and Riestra Menéndez, Sabino and González-Muñoza, Carlos and de Castro Parga, Luisa and Calvo Moya, Marta and Fuentes-Valenzuela, Esteban and Esteve, Maria and Iborra, Marisa and Dura Gil, Miguel and Barreiro-De Acosta, Manuel and Lorente-Poyatos, Rufo Humberto and Manceñido, Noemí and Calafat, Margalida and Rodríguez-Lago, Iago and Guardiola Capo, Jordi and Payeras, Maria Antonia and Morales Alvarado, Víctor Jair and Tardillo, Carlos and Bujanda, Luis and Muñoz-Nuñez, José Fernando and Ber Nieto, Yolanda and Bermejo, Fernando and Almela, Pedro and Navarro-Llavat, Mercè and Martínez Montiel, Pilar and Rodríguez Gutiérrez, Cristina and Van Domselaar, Manuel and Sesé, Eva and Martínez Pérez, Teresa and Ricart, Elena and Chaparro, María and García, María José and López-Sanromán, Antonio and Sicilia, Beatriz and Orts, Beatriz and López-García, Alicia and Martín-Arranz, Eduardo and Pérez-Calle, José Lázaro and de Francisco, Ruth and García-Planella, Esther and Domènech, Eugeni and García-López, y Santiago},\n\tmonth = aug,\n\tyear = {2022},\n\tpages = {jjac108},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/RZL9VKBX/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods: Elderly patients [\\textgreater60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. Results: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Conclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://doi.org/10.1096/fj.202200118RR\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022', 'https://doi.org/10.1096/fj.202200118RR', event);\">\n    Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Lopez-Yus, M.; Lorente-Cebrian, S.; del Moral-Bergos, R.; Hörndler, C.; Garcia-Sobreviela, M. P.; Casamayor, C.; Sanz-Paris, A.; Bernal-Monterde, V.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M</a>\n</span>\n\n  \n\n</span>\n\n  <i>The FASEB Journal</i>, 36(8): e22429. August 2022.\n  <span class=\"note\">Publisher: John Wiley & Sons, Ltd</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://doi.org/10.1096/fj.202200118RR\"\n     onclick=\"log_download('lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022', 'https://doi.org/10.1096/fj.202200118RR', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view\"\n     onclick=\"log_download('lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022', 'https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/https://doi.org/10.1096/fj.202200118RR\"\n     onclick=\"log_download('lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022', 'http://doi.org/https://doi.org/10.1096/fj.202200118RR', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lopezyus-lorentecebrian-delmoralbergos-hrndler-garciasobreviela-casamayor-sanzparis-bernalmonterde-etal-identificationofnoveltargetsinadiposetissueinvolvedinnonalcoholicfattyliverdiseaseprogression-2022')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{lopez-yus_identification_2022,\n\ttitle = {Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression},\n\tvolume = {36},\n\tcopyright = {All rights reserved},\n\tissn = {0892-6638},\n\turl = {https://doi.org/10.1096/fj.202200118RR},\n\tdoi = {https://doi.org/10.1096/fj.202200118RR},\n\tabstract = {Abstract Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.},\n\tnumber = {8},\n\tjournal = {The FASEB Journal},\n\tauthor = {Lopez-Yus, Marta and Lorente-Cebrian, Silvia and del Moral-Bergos, Raquel and Hörndler, Carlos and Garcia-Sobreviela, Maria Pilar and Casamayor, Carmen and Sanz-Paris, Alejandro and Bernal-Monterde, Vanesa and Arbones-Mainar, Jose M},\n\tmonth = aug,\n\tyear = {2022},\n\tnote = {Publisher: John Wiley \\&amp; Sons, Ltd},\n\tpages = {e22429},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/AAH8FJXZ/file/view}\n}\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Abstract Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2021\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2021')\"\n      onkeypress=\"toggleGroup('group_2021')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2021</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://doi.org/10.1007/s13105-021-00836-7\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021', 'https://doi.org/10.1007/s13105-021-00836-7', event);\">\n    Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Lopez-Yus, M.; Lopez-Perez, R.; Garcia-Sobreviela, M. P.; del Moral-Bergos, R.; Lorente-Cebrian, S.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Physiology and Biochemistry</i>, (0123456789).  2021.\n  <span class=\"note\">Publisher: Springer Netherlands ISBN: 0123456789</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://doi.org/10.1007/s13105-021-00836-7\"\n     onclick=\"log_download('lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021', 'https://doi.org/10.1007/s13105-021-00836-7', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view\"\n     onclick=\"log_download('lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021', 'https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s13105-021-00836-7\"\n     onclick=\"log_download('lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021', 'http://doi.org/10.1007/s13105-021-00836-7', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lopezyus-lopezperez-garciasobreviela-delmoralbergos-lorentecebrian-arbonesmainar-adiponectinoverexpressioninc2c12myocytesincreaseslipidoxidationandmyofibertransition-2021')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{lopez-yus_adiponectin_2021,\n\ttitle = {Adiponectin overexpression in {C2C12} myocytes increases lipid oxidation and myofiber transition},\n\tcopyright = {All rights reserved},\n\tissn = {18778755},\n\turl = {https://doi.org/10.1007/s13105-021-00836-7},\n\tdoi = {10.1007/s13105-021-00836-7},\n\tabstract = {Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.},\n\tnumber = {0123456789},\n\tjournal = {Journal of Physiology and Biochemistry},\n\tauthor = {Lopez-Yus, Marta and Lopez-Perez, Rebeca and Garcia-Sobreviela, Maria Pilar and del Moral-Bergos, Raquel and Lorente-Cebrian, Silvia and Arbones-Mainar, Jose M.},\n\tyear = {2021},\n\tnote = {Publisher: Springer Netherlands\nISBN: 0123456789},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/VVTUFZ8F/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2020\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2020')\"\n      onkeypress=\"toggleGroup('group_2020')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2020</span>\n      <span class=\"bibbase_group_count\">\n        \n        (5)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://www.mdpi.com/2227-9059/8/9/328\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020', 'https://www.mdpi.com/2227-9059/8/9/328', event);\">\n    SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Bernal-Monterde, V.; Casas-Deza, D.; Letona-Giménez, L.; de la Llama-Celis, N.; Calmarza, P.; Sierra-Gabarda, O.; Betoré-Glaria, E.; Martínez-de Lagos, M.; Martínez-Barredo, L.; Espinosa-Pérez, M.;  and M. Arbones-Mainar, J.\n</span>\n\n  \n\n</span>\n\n  <i>Biomedicines</i>, 8(9): 328.  2020.\n  <span class=\"note\">ISBN: 2227-9059</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://www.mdpi.com/2227-9059/8/9/328\"\n     onclick=\"log_download('bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020', 'https://www.mdpi.com/2227-9059/8/9/328', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view\"\n     onclick=\"log_download('bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020', 'https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3390/biomedicines8090328\"\n     onclick=\"log_download('bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020', 'http://doi.org/10.3390/biomedicines8090328', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('bernalmonterde-casasdeza-letonagimnez-delallamacelis-calmarza-sierragabarda-betorglaria-martnezdelagos-etal-sarscov2infectioninducesadualresponseinliverfunctiontestsassociationwithmortalityduringhospitalization-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Bernal-Monterde2020,\n\ttitle = {{SARS}-{CoV}-2 {Infection} {Induces} a {Dual} {Response} in {Liver} {Function} {Tests}: {Association} with {Mortality} during {Hospitalization}},\n\tvolume = {8},\n\tcopyright = {All rights reserved},\n\turl = {https://www.mdpi.com/2227-9059/8/9/328},\n\tdoi = {10.3390/biomedicines8090328},\n\tabstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5\\%) were discharged (109 (20.5\\%) died). A total of 319 (64.3\\%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9\\%) and GGT (47.3\\%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.},\n\tnumber = {9},\n\tjournal = {Biomedicines},\n\tauthor = {Bernal-Monterde, Vanesa and Casas-Deza, Diego and Letona-Giménez, Laura and de la Llama-Celis, Natalia and Calmarza, Pilar and Sierra-Gabarda, Olivia and Betoré-Glaria, Elena and Martínez-de Lagos, María and Martínez-Barredo, Lucía and Espinosa-Pérez, María and M. Arbones-Mainar, Jose},\n\tyear = {2020},\n\tnote = {ISBN: 2227-9059},\n\tpages = {328},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/J2SV7I3G/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020', 'https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view', event);\">\n    Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Martínez-Fernández, L.; González-Muniesa, P.; Sáinz, N.; Escoté, X.; Martínez, J. A.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>;  and Moreno-Aliaga, M. J.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Physiology and Biochemistry</i>.  2020.\n  <span class=\"note\">Publisher: Journal of Physiology and Biochemistry</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view\"\n     onclick=\"log_download('martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020', 'https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s13105-020-00775-9\"\n     onclick=\"log_download('martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020', 'http://doi.org/10.1007/s13105-020-00775-9', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('martnezfernndez-gonzlezmuniesa-sinz-escot-martnez-arbonesmainar-morenoaliaga-maresin1regulatesinsulinsignalinginhumanadipocytesaswellasinadiposetissueandmuscleofleanandobesemice-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Martinez-Fernandez2020,\n\ttitle = {Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice},\n\tcopyright = {All rights reserved},\n\tissn = {18778755},\n\tdoi = {10.1007/s13105-020-00775-9},\n\tabstract = {Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling.},\n\tjournal = {Journal of Physiology and Biochemistry},\n\tauthor = {Martínez-Fernández, L. and González-Muniesa, P. and Sáinz, N. and Escoté, X. and Martínez, J. A. and Arbones-Mainar, J. M. and Moreno-Aliaga, M. J.},\n\tyear = {2020},\n\tnote = {Publisher: Journal of Physiology and Biochemistry},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/UWRA33SR/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020', 'https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view', event);\">\n    Prevalence of Malnutrition and 1-Year All-Cause Mortality in Institutionalized Elderly Patients Comparing Different Combinations of the GLIM Criteria.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Sanz-Paris, A.; González Fernández, M.; Perez-Nogueras, J.; Serrano-Oliver, A.; Torres-Anoro, E.; Sanz-Arque, A.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Parenteral and Enteral Nutrition</i>.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view\"\n     onclick=\"log_download('sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020', 'https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Prevalence of Malnutrition and 1-Year All-Cause Mortality in Institutionalized Elderly Patients Comparing Different Combinations of the GLIM Criteria [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1002/jpen.2029\"\n     onclick=\"log_download('sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020', 'http://doi.org/10.1002/jpen.2029', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('sanzparis-gonzlezfernndez-pereznogueras-serranooliver-torresanoro-sanzarque-arbonesmainar-prevalenceofmalnutritionand1yearallcausemortalityininstitutionalizedelderlypatientscomparingdifferentcombinationsoftheglimcriteria-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Sanz-Paris2020,\n\ttitle = {Prevalence of {Malnutrition} and 1-{Year} {All}-{Cause} {Mortality} in {Institutionalized} {Elderly} {Patients} {Comparing} {Different} {Combinations} of the {GLIM} {Criteria}},\n\tcopyright = {All rights reserved},\n\tissn = {19412444},\n\tdoi = {10.1002/jpen.2029},\n\tabstract = {Background: The Global Leadership Initiative on Malnutrition (GLIM) provided a new approach for the diagnosis of malnutrition based on a number of phenotypic and etiologic criteria. However, different diagnostic criteria could potentially lead to heterogeneity in the diagnosis. We identified different subsets of criteria to define malnutrition in a cohort of elder nursing-home residents and investigated their clinical utility in terms of 1-year survival. Methods: Our study included all residents (n = 485) from 3 nursing homes. We proposed 12 GLIM models based on different phenotypic and etiologic criteria. The main outcome was 1-year all-cause mortality. We also assessed the sensitivity and specificity for different phenotypic criteria using time-dependent receiver operating characteristic curves, and cutoff values were calculated. Results: During 1 year of follow-ups, 94 deaths occurred. The prevalence of malnutrition was 13.5\\% for models based on reduced food intake (RFI) and 10.45\\% for models based on inflammation associated with acute disease (IAD). Unadjusted Cox regression analyses showed that malnutrition was associated with a 2.31- to 4.64-fold increase in mortality when diagnosed using IAD-dependent models or with a 1.37- to 1.78-fold increase in mortality using RFI-dependent models. Cutoffs associated with mortality for the phenotypic criteria were lower than those recommended in the GLIM criteria. Conclusion: This study describes the association of several variations of the GLIM model with 1-year mortality in nursing-home residents. However, our data suggest a high heterogeneity to fulfill the GLIM criteria and the necessity of finding specific, tailored cutoff points for the studied populations.},\n\tjournal = {Journal of Parenteral and Enteral Nutrition},\n\tauthor = {Sanz-Paris, Alejandro and González Fernández, Mikel and Perez-Nogueras, Javier and Serrano-Oliver, Antonio and Torres-Anoro, Elena and Sanz-Arque, Alejandro and Arbones-Mainar, Jose M.},\n\tyear = {2020},\n\tpmid = {33043987},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/9WQVYUSH/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Background: The Global Leadership Initiative on Malnutrition (GLIM) provided a new approach for the diagnosis of malnutrition based on a number of phenotypic and etiologic criteria. However, different diagnostic criteria could potentially lead to heterogeneity in the diagnosis. We identified different subsets of criteria to define malnutrition in a cohort of elder nursing-home residents and investigated their clinical utility in terms of 1-year survival. Methods: Our study included all residents (n = 485) from 3 nursing homes. We proposed 12 GLIM models based on different phenotypic and etiologic criteria. The main outcome was 1-year all-cause mortality. We also assessed the sensitivity and specificity for different phenotypic criteria using time-dependent receiver operating characteristic curves, and cutoff values were calculated. Results: During 1 year of follow-ups, 94 deaths occurred. The prevalence of malnutrition was 13.5% for models based on reduced food intake (RFI) and 10.45% for models based on inflammation associated with acute disease (IAD). Unadjusted Cox regression analyses showed that malnutrition was associated with a 2.31- to 4.64-fold increase in mortality when diagnosed using IAD-dependent models or with a 1.37- to 1.78-fold increase in mortality using RFI-dependent models. Cutoffs associated with mortality for the phenotypic criteria were lower than those recommended in the GLIM criteria. Conclusion: This study describes the association of several variations of the GLIM model with 1-year mortality in nursing-home residents. However, our data suggest a high heterogeneity to fulfill the GLIM criteria and the necessity of finding specific, tailored cutoff points for the studied populations.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"muozcabrejas-espinacadena-arbonesmainar-morenofranco-alteracionesdelmetabolismolipdicoproducidasporelvirusdelahepatitiscenpacientesconinfeccincrnica-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'muozcabrejas-espinacadena-arbonesmainar-morenofranco-alteracionesdelmetabolismolipdicoproducidasporelvirusdelahepatitiscenpacientesconinfeccincrnica-2020', 'https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view', event);\">\n    ALTERACIONES DEL METABOLISMO LIPÍDICO PRODUCIDAS POR EL VIRUS DE LA HEPATITIS C EN PACIENTES CON INFECCIÓN CRÓNICA.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Muñoz-Cabrejas, A.; Espina-Cadena, S.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>;  and Moreno-Franco, B.\n</span>\n\n  \n\n</span>\n\n  <i>Rev Esp Salud Pública</i>, 94: e1–15.  2020.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view\"\n     onclick=\"log_download('muozcabrejas-espinacadena-arbonesmainar-morenofranco-alteracionesdelmetabolismolipdicoproducidasporelvirusdelahepatitiscenpacientesconinfeccincrnica-2020', 'https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"ALTERACIONES DEL METABOLISMO LIPÍDICO PRODUCIDAS POR EL VIRUS DE LA HEPATITIS C EN PACIENTES CON INFECCIÓN CRÓNICA [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/muozcabrejas-espinacadena-arbonesmainar-morenofranco-alteracionesdelmetabolismolipdicoproducidasporelvirusdelahepatitiscenpacientesconinfeccincrnica-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('muozcabrejas-espinacadena-arbonesmainar-morenofranco-alteracionesdelmetabolismolipdicoproducidasporelvirusdelahepatitiscenpacientesconinfeccincrnica-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Munoz-Cabrejas2020,\n\ttitle = {{ALTERACIONES} {DEL} {METABOLISMO} {LIPÍDICO} {PRODUCIDAS} {POR} {EL} {VIRUS} {DE} {LA} {HEPATITIS} {C} {EN} {PACIENTES} {CON} {INFECCIÓN} {CRÓNICA}},\n\tvolume = {94},\n\tcopyright = {All rights reserved},\n\tjournal = {Rev Esp Salud Pública},\n\tauthor = {Muñoz-Cabrejas, Ainara and Espina-Cadena, Silvia and Arbones-Mainar, José Miguel and Moreno-Franco, Belén},\n\tyear = {2020},\n\tpages = {e1--15},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/DE4SQLBN/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32087284\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32087284', event);\">\n    Beyond the CNS: The many peripheral roles of APOE.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Martinez-Martínez, A. B; Torres-Perez, E.; Devanney, N.; Del Moral, R.; Johnson, L. A;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M</a>\n</span>\n\n  \n\n</span>\n\n  <i>Neurobiology of disease</i>, 138(November 2019): 104809.  2020.\n  <span class=\"note\">Publisher: Elsevier</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/32087284\"\n     onclick=\"log_download('martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020', 'http://www.ncbi.nlm.nih.gov/pubmed/32087284', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Beyond the CNS: The many peripheral roles of APOE. [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view\"\n     onclick=\"log_download('martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020', 'https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Beyond the CNS: The many peripheral roles of APOE. [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nbd.2020.104809\"\n     onclick=\"log_download('martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020', 'http://doi.org/10.1016/j.nbd.2020.104809', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('martinezmartnez-torresperez-devanney-delmoral-johnson-arbonesmainar-beyondthecnsthemanyperipheralrolesofapoe-2020')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Martinez-Martinez2020,\n\ttitle = {Beyond the {CNS}: {The} many peripheral roles of {APOE}.},\n\tvolume = {138},\n\tcopyright = {All rights reserved},\n\tissn = {1095-953X},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/32087284},\n\tdoi = {10.1016/j.nbd.2020.104809},\n\tabstract = {Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75\\% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer&#x27;s disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.},\n\tnumber = {November 2019},\n\tjournal = {Neurobiology of disease},\n\tauthor = {Martinez-Martínez, Ana B and Torres-Perez, Elena and Devanney, Nicholas and Del Moral, Raquel and Johnson, Lance A and Arbones-Mainar, Jose M},\n\tyear = {2020},\n\tpmid = {32087284},\n\tnote = {Publisher: Elsevier},\n\tpages = {104809},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/SUY8JK4N/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2019\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2019')\"\n      onkeypress=\"toggleGroup('group_2019')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2019</span>\n      <span class=\"bibbase_group_count\">\n        \n        (4)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019', 'https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view', event);\">\n    Are Comorbidities Associated With Overall Survival in Patients With Oral Squamous Cell Carcinoma?.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Jariod-Ferrer, Ú. M.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>; Gavin-Clavero, M. A.; Simón-Sanz, M. V.; Moral-Saez, I.; Cisneros-Gimeno, A. I.;  and Martinez-Trufero, J.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Oral and Maxillofacial Surgery</i>, 77(9): 1906–1914.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view\"\n     onclick=\"log_download('jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019', 'https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Are Comorbidities Associated With Overall Survival in Patients With Oral Squamous Cell Carcinoma? [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.joms.2019.03.007\"\n     onclick=\"log_download('jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019', 'http://doi.org/10.1016/j.joms.2019.03.007', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('jariodferrer-arbonesmainar-gavinclavero-simnsanz-moralsaez-cisnerosgimeno-martineztrufero-arecomorbiditiesassociatedwithoverallsurvivalinpatientswithoralsquamouscellcarcinoma-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Jariod-Ferrer2019,\n\ttitle = {Are {Comorbidities} {Associated} {With} {Overall} {Survival} in {Patients} {With} {Oral} {Squamous} {Cell} {Carcinoma}?},\n\tvolume = {77},\n\tcopyright = {All rights reserved},\n\tissn = {15315053},\n\tdoi = {10.1016/j.joms.2019.03.007},\n\tabstract = {Purpose: Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods: A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results: Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion: These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC.},\n\tnumber = {9},\n\tjournal = {Journal of Oral and Maxillofacial Surgery},\n\tauthor = {Jariod-Ferrer, Úrsula M. and Arbones-Mainar, Jose M. and Gavin-Clavero, Marina A. and Simón-Sanz, M. Victoria and Moral-Saez, Ignacio and Cisneros-Gimeno, Ana I. and Martinez-Trufero, Javier},\n\tyear = {2019},\n\tpages = {1906--1914},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/KFL6FEA7/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Purpose: Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods: A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results: Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion: These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"giliturbe-arbonesmainar-morenoaliaga-lostao-glut12andadiposetissueexpressionregulationanditsrelationwithobesityinmice-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  GLUT12 and adipose tissue: Expression, regulation and its relation with obesity in mice.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Gil-Iturbe, E.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>; Moreno-Aliaga, M. J.;  and Lostao, M. P.\n</span>\n\n  \n\n</span>\n\n  <i>Acta Physiologica</i>, (April): 1–14.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1111/apha.13283\"\n     onclick=\"log_download('giliturbe-arbonesmainar-morenoaliaga-lostao-glut12andadiposetissueexpressionregulationanditsrelationwithobesityinmice-2019', 'http://doi.org/10.1111/apha.13283', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/giliturbe-arbonesmainar-morenoaliaga-lostao-glut12andadiposetissueexpressionregulationanditsrelationwithobesityinmice-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('giliturbe-arbonesmainar-morenoaliaga-lostao-glut12andadiposetissueexpressionregulationanditsrelationwithobesityinmice-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Gil-Iturbe2019,\n\ttitle = {{GLUT12} and adipose tissue: {Expression}, regulation and its relation with obesity in mice},\n\tcopyright = {All rights reserved},\n\tissn = {17481716},\n\tdoi = {10.1111/apha.13283},\n\tabstract = {AIM The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. METHODS Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. RESULTS GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. CONCLUSION We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.},\n\tnumber = {April},\n\tjournal = {Acta Physiologica},\n\tauthor = {Gil-Iturbe, Eva and Arbones-Mainar, José Miguel and Moreno-Aliaga, María J. and Lostao, María Pilar},\n\tyear = {2019},\n\tpages = {1--14},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  AIM The facilitative glucose transporter GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. GLUT12 is expressed in insulin-sensitive tissues such as adipose tissue. The aim of this work was to investigate GLUT12 expression and hormonal regulation in 3T3-L1 adipocytes and in adipose tissue of lean and diet-induced obese mice. METHODS Uptake studies were performed using radio-labelled sugars; α-methyl-d-glucose (αMG) was used as specific substrate of GLUT12. Expression and localization of GLUT12 in adipocytes were investigated by western blot and immunohistochemical methods. RESULTS GLUT12 is expressed in the peri-nuclear region of mouse adipocytes. Insulin, by AKT activation, and TNF-α, by AMPK activation, increase αMG uptake by inducing GLUT12 translocation to the membrane. In contrast, leptin and adiponectin decrease GLUT12 activity through its internalization. Under hypoxia conditions GLUT12 expression is upregulated. The response of GLUT12 to TNF-α, leptin, adiponectin and hypoxia is the opposite to that of GLUT4. In diet-induced obese mice and obese subjects, GLUT12 protein is decreased. Intraperitoneal injection of insulin increases AKT phosphorylation and GLUT12 expression, but this effect is lost in obese animals. CONCLUSION We hypothesize that GLUT12 would contribute to modulate sugar absorption in physiological and pathophysiological situations such as obesity.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019', 'https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view', event);\">\n    Neck circumference is associated with nutritional status in elderly nursing home residents.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Serrano-Oliver, A.; Torres-Anoro, E.; Lardiés-Sanchez, B.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>; Sanz-Paris, A.;  and Perez-Nogueras, J.\n</span>\n\n  \n\n</span>\n\n  <i>Nutrition</i>, 62: 153–157.  2019.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view\"\n     onclick=\"log_download('serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019', 'https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Neck circumference is associated with nutritional status in elderly nursing home residents [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.nut.2019.01.015\"\n     onclick=\"log_download('serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019', 'http://doi.org/10.1016/j.nut.2019.01.015', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('serranooliver-torresanoro-lardissanchez-arbonesmainar-sanzparis-pereznogueras-neckcircumferenceisassociatedwithnutritionalstatusinelderlynursinghomeresidents-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Serrano-Oliver2019,\n\ttitle = {Neck circumference is associated with nutritional status in elderly nursing home residents},\n\tvolume = {62},\n\tcopyright = {All rights reserved},\n\tissn = {08999007},\n\tdoi = {10.1016/j.nut.2019.01.015},\n\tjournal = {Nutrition},\n\tauthor = {Serrano-Oliver, Antonio and Torres-Anoro, Elena and Lardiés-Sanchez, Beatriz and Arbones-Mainar, Jose M. and Sanz-Paris, Alejandro and Perez-Nogueras, Javier},\n\tyear = {2019},\n\tpages = {153--157},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/E5A2RG8N/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"leroux-lemery-boulet-briot-zakaroff-bouloumi-andrade-prezmatute-etal-effectsoftheaminoacidderivativeshydroxymethylbutyratetaurineandnmethyltyramineontriacylglycerolbreakdowninfatcells-2019\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'leroux-lemery-boulet-briot-zakaroff-bouloumi-andrade-prezmatute-etal-effectsoftheaminoacidderivativeshydroxymethylbutyratetaurineandnmethyltyramineontriacylglycerolbreakdowninfatcells-2019', 'https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view', event);\">\n    Effects of the amino acid derivatives , β -hydroxy- β -methylbutyrate , taurine , and N-methyltyramine , on triacylglycerol breakdown in fat cells.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Leroux, M.; Lemery, T.; Boulet, N.; Briot, A.; Zakaroff, A.; Bouloumié, A.; Andrade, F.; Pérez-matute, P.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-mainar, J. M</a>;  and Carpéné, C.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Physiology and Biochemistry</i>.  2019.\n  <span class=\"note\">Publisher: Journal of Physiology and Biochemistry</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view\"\n     onclick=\"log_download('leroux-lemery-boulet-briot-zakaroff-bouloumi-andrade-prezmatute-etal-effectsoftheaminoacidderivativeshydroxymethylbutyratetaurineandnmethyltyramineontriacylglycerolbreakdowninfatcells-2019', 'https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Effects of the amino acid derivatives , β -hydroxy- β -methylbutyrate , taurine , and N-methyltyramine , on triacylglycerol breakdown in fat cells [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/leroux-lemery-boulet-briot-zakaroff-bouloumi-andrade-prezmatute-etal-effectsoftheaminoacidderivativeshydroxymethylbutyratetaurineandnmethyltyramineontriacylglycerolbreakdowninfatcells-2019\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('leroux-lemery-boulet-briot-zakaroff-bouloumi-andrade-prezmatute-etal-effectsoftheaminoacidderivativeshydroxymethylbutyratetaurineandnmethyltyramineontriacylglycerolbreakdowninfatcells-2019')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Leroux2019,\n\ttitle = {Effects of the amino acid derivatives , β -hydroxy- β -methylbutyrate , taurine , and {N}-methyltyramine , on triacylglycerol breakdown in fat cells},\n\tcopyright = {All rights reserved},\n\tjournal = {Journal of Physiology and Biochemistry},\n\tauthor = {Leroux, Mélanie and Lemery, Tristan and Boulet, Nathalie and Briot, Anaïs and Zakaroff, Alexia and Bouloumié, Anne and Andrade, Fernando and Pérez-matute, Patricia and Arbones-mainar, Jose M and Carpéné, Christian},\n\tyear = {2019},\n\tnote = {Publisher: Journal of Physiology and Biochemistry},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/WBJ6HTUH/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2018\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2018')\"\n      onkeypress=\"toggleGroup('group_2018')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2018</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.mdpi.com/1422-0067/19/7/2081\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018', 'http://www.mdpi.com/1422-0067/19/7/2081', event);\">\n    The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Carpéné, C.; Pejenaute, H.; del Moral, R.; Boulet, N.; Hijona, E.; Andrade, F.; Villanueva-Millán, J M.; Aguirre, L.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>; Villanueva-Millán, M.; Aguirre, L.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>International Journal of Molecular Sciences</i>, 19(7): 2081.  2018.\n  <span class=\"note\">ISBN: 1422-0067</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.mdpi.com/1422-0067/19/7/2081\"\n     onclick=\"log_download('carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018', 'http://www.mdpi.com/1422-0067/19/7/2081', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.3390/ijms19072081\"\n     onclick=\"log_download('carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018', 'http://doi.org/10.3390/ijms19072081', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('carpn-pejenaute-delmoral-boulet-hijona-andrade-villanuevamilln-aguirre-etal-thedietaryantioxidantpiceatannolinhibitsadipogenesisofhumanadiposemesenchymalstemcellsandlimitsglucosetransportandlipogenicactivitiesinadipocytes-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Carpene2018,\n\ttitle = {The {Dietary} {Antioxidant} {Piceatannol} {Inhibits} {Adipogenesis} of {Human} {Adipose} {Mesenchymal} {Stem} {Cells} and {Limits} {Glucose} {Transport} and {Lipogenic} {Activities} in {Adipocytes}},\n\tvolume = {19},\n\tcopyright = {All rights reserved},\n\tissn = {1422-0067},\n\turl = {http://www.mdpi.com/1422-0067/19/7/2081},\n\tdoi = {10.3390/ijms19072081},\n\tabstract = {Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty μM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.},\n\tnumber = {7},\n\tjournal = {International Journal of Molecular Sciences},\n\tauthor = {Carpéné, Christian and Pejenaute, Héctor and del Moral, Raquel and Boulet, Nathalie and Hijona, Elizabeth and Andrade, Fernando and Villanueva-Millán, J Maria and Aguirre, Leixuri and Arbones-Mainar, José Miguel and Villanueva-Millán, Maria and Aguirre, Leixuri and Arbones-Mainar, José Miguel},\n\tyear = {2018},\n\tnote = {ISBN: 1422-0067},\n\tpages = {2081},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty μM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://link.springer.com/10.1007/s13105-018-0638-9\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018', 'http://link.springer.com/10.1007/s13105-018-0638-9', event);\">\n    PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Perez-Diaz, S.; Garcia-Sobreviela, M. P.; Gonzalez-Irazabal, Y.; Garcia-Rodriguez, B.; Espina, S.; Arenaz, I.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Physiology and Biochemistry</i>.  2018.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://link.springer.com/10.1007/s13105-018-0638-9\"\n     onclick=\"log_download('perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018', 'http://link.springer.com/10.1007/s13105-018-0638-9', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view\"\n     onclick=\"log_download('perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018', 'https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s13105-018-0638-9\"\n     onclick=\"log_download('perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018', 'http://doi.org/10.1007/s13105-018-0638-9', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('perezdiaz-garciasobreviela-gonzalezirazabal-garciarodriguez-espina-arenaz-arbonesmainar-ptrfactsasanadipokinecontributingtoadipocytedysfunctionalityandectopiclipiddeposition-2018')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Perez-Diaz2018,\n\ttitle = {{PTRF} acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition},\n\tcopyright = {All rights reserved},\n\tissn = {1138-7548},\n\turl = {http://link.springer.com/10.1007/s13105-018-0638-9},\n\tdoi = {10.1007/s13105-018-0638-9},\n\tjournal = {Journal of Physiology and Biochemistry},\n\tauthor = {Perez-Diaz, Sergio and Garcia-Sobreviela, Maria P. and Gonzalez-Irazabal, Yolanda and Garcia-Rodriguez, Beatriz and Espina, Silvia and Arenaz, Izaskun and Arbones-Mainar, Jose M.},\n\tyear = {2018},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/VW6CK532/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2017\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2017')\"\n      onkeypress=\"toggleGroup('group_2017')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2017</span>\n      <span class=\"bibbase_group_count\">\n        \n        (4)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"sanzparis-rodriguezvalle-navarro-puzofoncillas-arbonesmainar-postlunchtriglyceridaemiaassociateswithhdlcandinsulinresistanceinfastingnormotriglyceridaemicmenopausalwomen-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Post-lunch triglyceridaemia associates with HDLc and insulin resistance in fasting normotriglyceridaemic menopausal women.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Sanz-Paris, A.; Rodriguez-Valle, A.; Navarro, M. A.; Puzo-Foncillas, J.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Human Nutrition and Dietetics</i>,700–708.  2017.\n  <span class=\"note\">Volume: 30 Issue: 6</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1111/jhn.12476\"\n     onclick=\"log_download('sanzparis-rodriguezvalle-navarro-puzofoncillas-arbonesmainar-postlunchtriglyceridaemiaassociateswithhdlcandinsulinresistanceinfastingnormotriglyceridaemicmenopausalwomen-2017', 'http://doi.org/10.1111/jhn.12476', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/sanzparis-rodriguezvalle-navarro-puzofoncillas-arbonesmainar-postlunchtriglyceridaemiaassociateswithhdlcandinsulinresistanceinfastingnormotriglyceridaemicmenopausalwomen-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('sanzparis-rodriguezvalle-navarro-puzofoncillas-arbonesmainar-postlunchtriglyceridaemiaassociateswithhdlcandinsulinresistanceinfastingnormotriglyceridaemicmenopausalwomen-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Sanz-Paris2017,\n\ttitle = {Post-lunch triglyceridaemia associates with {HDLc} and insulin resistance in fasting normotriglyceridaemic menopausal women},\n\tcopyright = {All rights reserved},\n\tissn = {1365277X},\n\tabstract = {© 2017 The British Dietetic Association Ltd. Objectives: Post-prandial hypertriglyceridaemia (P-HTG) is associated with cardiovascular disease. This association is of paramount importance during menopause, which is also related to reduced high-density lipoprotein-cholesterol (HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at fasting and adhered to a Mediterranean-style eating pattern. Methods: We performed oral fat loading tests (OFLT) in combination with self-measurements of diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women. TG levels {\\textgreater} 220 mg dL -1 at any given time during the OFLT served as diagnostic criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to classify these women as having P-HTG according to the OFLT. Insulin resistance was defined as the upper tertile of the homeostatic model assessment of insulin resistance. Results: We found that, despite having normal fasting TG levels, P-HTG was highly prevalent (approximately 40\\%). Moreover, self-assessed 3-h post-lunch TG levels {\\textgreater} 165 mg dL -1 increased the odds of having hypo-HDL cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women adhering to a Mediterranean eating pattern having their highest energy intake at lunch. Conclusions: Self-assessed 3-h post-lunch TG can be used to study post-prandial TG metabolism in Southern European menopausal women who are normotriglyceridaemic at fasting. Characterising an individual&#x27;s post-prandial response may help menopausal women to evaluate their risk of cardiovascular disease.},\n\tjournal = {Journal of Human Nutrition and Dietetics},\n\tauthor = {Sanz-Paris, A. and Rodriguez-Valle, A. and Navarro, M. A. and Puzo-Foncillas, J. and Arbones-Mainar, J. M.},\n\tyear = {2017},\n\tdoi = {10.1111/jhn.12476},\n\tnote = {Volume: 30\nIssue: 6},\n\tpages = {700--708},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  © 2017 The British Dietetic Association Ltd. Objectives: Post-prandial hypertriglyceridaemia (P-HTG) is associated with cardiovascular disease. This association is of paramount importance during menopause, which is also related to reduced high-density lipoprotein-cholesterol (HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at fasting and adhered to a Mediterranean-style eating pattern. Methods: We performed oral fat loading tests (OFLT) in combination with self-measurements of diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women. TG levels \\textgreater 220 mg dL -1 at any given time during the OFLT served as diagnostic criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to classify these women as having P-HTG according to the OFLT. Insulin resistance was defined as the upper tertile of the homeostatic model assessment of insulin resistance. Results: We found that, despite having normal fasting TG levels, P-HTG was highly prevalent (approximately 40%). Moreover, self-assessed 3-h post-lunch TG levels \\textgreater 165 mg dL -1 increased the odds of having hypo-HDL cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women adhering to a Mediterranean eating pattern having their highest energy intake at lunch. Conclusions: Self-assessed 3-h post-lunch TG can be used to study post-prandial TG metabolism in Southern European menopausal women who are normotriglyceridaemic at fasting. Characterising an individual's post-prandial response may help menopausal women to evaluate their risk of cardiovascular disease.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"llobet-bayonabafaluy-pacheugrau-torresprez-arbonesmainar-navarro-gmezdaz-montoya-etal-pharmacologicconcentrationsoflinezolidmodifyoxidativephosphorylationfunctionandadipocytesecretome-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Llobet, L.; Bayona-Bafaluy, M.; Pacheu-Grau, D.; Torres-Pérez, E.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Navarro, M.; Gómez-Díaz, C.; Montoya, J.; López-Gallardo, E.;  and Ruiz-Pesini, E.\n</span>\n\n  \n\n</span>\n\n  <i>Redox Biology</i>, 13.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.redox.2017.05.026\"\n     onclick=\"log_download('llobet-bayonabafaluy-pacheugrau-torresprez-arbonesmainar-navarro-gmezdaz-montoya-etal-pharmacologicconcentrationsoflinezolidmodifyoxidativephosphorylationfunctionandadipocytesecretome-2017', 'http://doi.org/10.1016/j.redox.2017.05.026', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/llobet-bayonabafaluy-pacheugrau-torresprez-arbonesmainar-navarro-gmezdaz-montoya-etal-pharmacologicconcentrationsoflinezolidmodifyoxidativephosphorylationfunctionandadipocytesecretome-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('llobet-bayonabafaluy-pacheugrau-torresprez-arbonesmainar-navarro-gmezdaz-montoya-etal-pharmacologicconcentrationsoflinezolidmodifyoxidativephosphorylationfunctionandadipocytesecretome-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Llobet2017,\n\ttitle = {Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome},\n\tvolume = {13},\n\tcopyright = {All rights reserved},\n\tissn = {22132317},\n\tdoi = {10.1016/j.redox.2017.05.026},\n\tabstract = {© 2017 The Authors The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.},\n\tjournal = {Redox Biology},\n\tauthor = {Llobet, L. and Bayona-Bafaluy, M.P. and Pacheu-Grau, D. and Torres-Pérez, E. and Arbones-Mainar, J.M. and Navarro, M.Á. and Gómez-Díaz, C. and Montoya, J. and López-Gallardo, E. and Ruiz-Pesini, E.},\n\tyear = {2017},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  © 2017 The Authors The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017', 'https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view', event);\">\n    Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Martinez-Fernandez, L.; Gonzalez-Muniesa, P.; Laiglesia, L. M; Sainz, N.; Prieto-Hontoria, P. L; Escote, X.; Odriozola, L.; Corrales, F. J; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M</a>; Martinez, J. A;  and Moreno-Aliaga, M. J\n</span>\n\n  \n\n</span>\n\n  <i>FASEB J.</i>.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view\"\n     onclick=\"log_download('martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017', 'https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1096/fj.201600859R\"\n     onclick=\"log_download('martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017', 'http://doi.org/10.1096/fj.201600859R', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('martinezfernandez-gonzalezmuniesa-laiglesia-sainz-prietohontoria-escote-odriozola-corrales-etal-maresin1improvesinsulinsensitivityandattenuatesadiposetissueinflammationin-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Mart2017,\n\ttitle = {Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in},\n\tcopyright = {All rights reserved},\n\tdoi = {10.1096/fj.201600859R},\n\tjournal = {FASEB J.},\n\tauthor = {Martinez-Fernandez, Leyre and Gonzalez-Muniesa, Pedro and Laiglesia, Laura M and Sainz, Neira and Prieto-Hontoria, Pedro L and Escote, Xavier and Odriozola, Leticia and Corrales, Fernando J and Arbones-Mainar, Jose M and Martinez, Jose A and Moreno-Aliaga, Maria J},\n\tyear = {2017},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/W5NPI5WE/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017', 'http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016', event);\">\n    Knock-down of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Perez-Diaz, S.; Garcia-Rodriguez, B.; Gonzalez-Irazabal, Y.; Valero, M.; Lagos-Lizan, J.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>\n</span>\n\n  \n\n</span>\n\n  <i>American Journal of Physiology - Cell Physiology</i>, (312): C83–C91.  2017.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016\"\n     onclick=\"log_download('perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017', 'http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Knock-down of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells. [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view\"\n     onclick=\"log_download('perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017', 'https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Knock-down of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells. [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1152/ajpcell.00246.2016\"\n     onclick=\"log_download('perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017', 'http://doi.org/10.1152/ajpcell.00246.2016', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('perezdiaz-garciarodriguez-gonzalezirazabal-valero-lagoslizan-arbonesmainar-knockdownofptrfamelioratesadipocytedifferentiationandfunctionalityofhumanmesenchymalstemcells-2017')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Perez-Diaz2016a,\n\ttitle = {Knock-down of {PTRF} ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells.},\n\tcopyright = {All rights reserved},\n\tissn = {0363-6143},\n\turl = {http://ajpcell.physiology.org/lookup/doi/10.1152/ajpcell.00246.2016},\n\tdoi = {10.1152/ajpcell.00246.2016},\n\tnumber = {312},\n\tjournal = {American Journal of Physiology - Cell Physiology},\n\tauthor = {Perez-Diaz, Sergio and Garcia-Rodriguez, Beatriz and Gonzalez-Irazabal, Yolanda and Valero, Monica and Lagos-Lizan, Javier and Arbones-Mainar, JM},\n\tyear = {2017},\n\tpages = {C83--C91},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/JGZ39E8F/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2016\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2016')\"\n      onkeypress=\"toggleGroup('group_2016')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2016</span>\n      <span class=\"bibbase_group_count\">\n        \n        (7)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://link.springer.com/10.1007/s13105-015-0464-2\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016', 'http://link.springer.com/10.1007/s13105-015-0464-2', event);\">\n    Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Hijona, E.; Aguirre, L.; Pérez-Matute, P.; Villanueva-Millán, M. J.; Mosqueda-Solis, A.; Hasnaoui, M.; Nepveu, F.; Senard, J. M.; Bujanda, L.; Aldámiz-Echevarría, L.; Llarena, M.; Andrade, F.; Perio, P.; Leboulanger, F.; Hijona, L.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>; Portillo, M.;  and Carpéné, C.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of physiology and biochemistry</i>, (72): 567–582.  2016.\n  <span class=\"note\">Publisher: Springer Netherlands</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://link.springer.com/10.1007/s13105-015-0464-2\"\n     onclick=\"log_download('hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016', 'http://link.springer.com/10.1007/s13105-015-0464-2', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view\"\n     onclick=\"log_download('hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016', 'https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s13105-015-0464-2\"\n     onclick=\"log_download('hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016', 'http://doi.org/10.1007/s13105-015-0464-2', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('hijona-aguirre-prezmatute-villanuevamilln-mosquedasolis-hasnaoui-nepveu-senard-etal-limitedbeneficialeffectsofpiceatannolsupplementationonobesitycomplicationsintheobesezuckerratgutmicrobiotametabolicendocrineandcardiacaspects-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Hijona2016a,\n\ttitle = {Limited beneficial effects of piceatannol supplementation on obesity complications in the obese {Zucker} rat: gut microbiota, metabolic, endocrine, and cardiac aspects},\n\tcopyright = {All rights reserved},\n\tissn = {1138-7548},\n\turl = {http://link.springer.com/10.1007/s13105-015-0464-2},\n\tdoi = {10.1007/s13105-015-0464-2},\n\tnumber = {72},\n\tjournal = {Journal of physiology and biochemistry},\n\tauthor = {Hijona, E. and Aguirre, L. and Pérez-Matute, P. and Villanueva-Millán, M. J. and Mosqueda-Solis, A. and Hasnaoui, M. and Nepveu, F. and Senard, J. M. and Bujanda, L. and Aldámiz-Echevarría, L. and Llarena, M. and Andrade, F. and Perio, P. and Leboulanger, F. and Hijona, L. and Arbones-Mainar, J. M. and Portillo, M.P. and Carpéné, C.},\n\tyear = {2016},\n\tnote = {Publisher: Springer Netherlands},\n\tpages = {567--582},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/JKNSGQHI/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"lesparellada-deleruyelle-cassagnes-boutin-balogh-arbonesmainar-biron-marceau-etal-piceatannolandresveratrolshareinhibitoryeffectsonhydrogenperoxidereleasemonoamineoxidaseandlipogenicactivitiesinadiposetissuebutdifferintheirantilipolyticproperties-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Les Parellada, F.; Deleruyelle, S.; Cassagnes, L.; Boutin, J.; Balogh, B.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Biron, S.; Marceau, P.; Richard, D.; Nepveu, F.; Mauriège, P.;  and Carpéné, C.\n</span>\n\n  \n\n</span>\n\n  <i>Chemico-Biological Interactions</i>, 258.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.cbi.2016.07.014\"\n     onclick=\"log_download('lesparellada-deleruyelle-cassagnes-boutin-balogh-arbonesmainar-biron-marceau-etal-piceatannolandresveratrolshareinhibitoryeffectsonhydrogenperoxidereleasemonoamineoxidaseandlipogenicactivitiesinadiposetissuebutdifferintheirantilipolyticproperties-2016', 'http://doi.org/10.1016/j.cbi.2016.07.014', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/lesparellada-deleruyelle-cassagnes-boutin-balogh-arbonesmainar-biron-marceau-etal-piceatannolandresveratrolshareinhibitoryeffectsonhydrogenperoxidereleasemonoamineoxidaseandlipogenicactivitiesinadiposetissuebutdifferintheirantilipolyticproperties-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('lesparellada-deleruyelle-cassagnes-boutin-balogh-arbonesmainar-biron-marceau-etal-piceatannolandresveratrolshareinhibitoryeffectsonhydrogenperoxidereleasemonoamineoxidaseandlipogenicactivitiesinadiposetissuebutdifferintheirantilipolyticproperties-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{les_parellada_piceatannol_2016,\n\ttitle = {Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties},\n\tvolume = {258},\n\tcopyright = {All rights reserved},\n\tissn = {18727786},\n\tdoi = {10.1016/j.cbi.2016.07.014},\n\tabstract = {© 2016 Elsevier Ireland Ltd Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release w as measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC 50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone – or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.},\n\tjournal = {Chemico-Biological Interactions},\n\tauthor = {Les Parellada, F. and Deleruyelle, S. and Cassagnes, L.-E. and Boutin, J.A. and Balogh, B. and Arbones-Mainar, J.M. and Biron, S. and Marceau, P. and Richard, D. and Nepveu, F. and Mauriège, P. and Carpéné, C.},\n\tyear = {2016},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  © 2016 Elsevier Ireland Ltd Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release w as measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC 50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone – or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://dx.doi.org/10.1007/s13105-015-0457-1\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016', 'http://dx.doi.org/10.1007/s13105-015-0457-1', event);\">\n    Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Llarena, M.; Andrade, F.; Hasnaoui, M.; Portillo, M.; Pérez-Matute, P.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Hijona, E.; Villanueva-Millán, M.; Aguirre, L.; Carpéné, C.;  and Aldámiz-Echevarría, L.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Physiology and Biochemistry</i>, 72(3): 555–566.  2016.\n  <span class=\"note\">Publisher: Springer Netherlands</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://dx.doi.org/10.1007/s13105-015-0457-1\"\n     onclick=\"log_download('llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016', 'http://dx.doi.org/10.1007/s13105-015-0457-1', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view\"\n     onclick=\"log_download('llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016', 'https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s13105-015-0457-1\"\n     onclick=\"log_download('llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016', 'http://doi.org/10.1007/s13105-015-0457-1', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('llarena-andrade-hasnaoui-portillo-prezmatute-arbonesmainar-hijona-villanuevamilln-etal-potentialrenoprotectiveeffectsofpiceatannolinamelioratingtheearlystagenephropathyassociatedwithobesityinobesezuckerrats-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Llarena2015,\n\ttitle = {Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese {Zucker} rats},\n\tvolume = {72},\n\tcopyright = {All rights reserved},\n\tissn = {1138-7548},\n\turl = {http://dx.doi.org/10.1007/s13105-015-0457-1},\n\tdoi = {10.1007/s13105-015-0457-1},\n\tlanguage = {English},\n\tnumber = {3},\n\tjournal = {Journal of Physiology and Biochemistry},\n\tauthor = {Llarena, Marta and Andrade, Fernando and Hasnaoui, Mounia and Portillo, MaríaP. and Pérez-Matute, Patricia and Arbones-Mainar, JoseM. and Hijona, Elizabeth and Villanueva-Millán, MaríaJesús and Aguirre, Leixuri and Carpéné, Christian and Aldámiz-Echevarría, Luis},\n\tyear = {2016},\n\tnote = {Publisher: Springer Netherlands},\n\tpages = {555--566},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/EA4IS7SX/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://dx.doi.org/10.1038/ijo.2016.93\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016', 'http://dx.doi.org/10.1038/ijo.2016.93', event);\">\n    Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Arbones-Mainar, J M; Johnson, L A; Torres-Perez, E; Garcia, A E; Perez-Diaz, S; Raber, J;  and Maeda, N\n</span>\n\n  \n\n</span>\n\n  Macmillan Publishers Limited, May 2016.\n  <span class=\"note\">Publication Title: Int J Obes</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://dx.doi.org/10.1038/ijo.2016.93\"\n     onclick=\"log_download('arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016', 'http://dx.doi.org/10.1038/ijo.2016.93', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4 [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view\"\n     onclick=\"log_download('arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016', 'https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4 [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('arbonesmainar-johnson-torresperez-garcia-perezdiaz-raber-maeda-metabolicshiftstowardsfattyacidusageandincreasedthermogenesisareassociatedwithimpairedadipogenesisinmiceexpressinghumanapoe4-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@book{Arbones-Mainar2016,\n\ttitle = {Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human {APOE4}},\n\tcopyright = {All rights reserved},\n\tisbn = {1476-5497},\n\turl = {http://dx.doi.org/10.1038/ijo.2016.93},\n\tpublisher = {Macmillan Publishers Limited},\n\tauthor = {Arbones-Mainar, J M and Johnson, L A and Torres-Perez, E and Garcia, A E and Perez-Diaz, S and Raber, J and Maeda, N},\n\tmonth = may,\n\tyear = {2016},\n\tnote = {Publication Title: Int J Obes},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/IWTXZZ5D/file/view}\n}\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://dx.doi.org/10.1016/j.fertnstert.2016.02.021\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016', 'http://dx.doi.org/10.1016/j.fertnstert.2016.02.021', event);\">\n    Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Gamundi-Segura, S.; Torres-Perez, E.; Sanz-Paris, A.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Fertility and Sterility</i>, 105(6): 1554–1560.e1. March 2016.\n  <span class=\"note\">Publisher: Elsevier</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://dx.doi.org/10.1016/j.fertnstert.2016.02.021\"\n     onclick=\"log_download('gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016', 'http://dx.doi.org/10.1016/j.fertnstert.2016.02.021', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view\"\n     onclick=\"log_download('gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016', 'https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.fertnstert.2016.02.021\"\n     onclick=\"log_download('gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016', 'http://doi.org/10.1016/j.fertnstert.2016.02.021', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('gamundisegura-torresperez-sanzparis-arbonesmainar-interactionofapolipoproteinegenepolymorphismsonmiscarriageriskinblackandwhiteamericanwomen-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Gamundi-Segura2016,\n\ttitle = {Interaction of apolipoprotein {E} gene polymorphisms on miscarriage risk in black and white {American} women},\n\tvolume = {105},\n\tcopyright = {All rights reserved},\n\tissn = {15565653},\n\turl = {http://dx.doi.org/10.1016/j.fertnstert.2016.02.021},\n\tdoi = {10.1016/j.fertnstert.2016.02.021},\n\tabstract = {Objective To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. Design Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations. Setting Not applicable. Patient(s) Women without miscarriages (controls) and women who miscarried at least once (cases). Intervention(s) None. Main Outcome Measure(s) A group of women (n = 1,372) successfully followed for 25??years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. Result(s) In white women followed up for 25??years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95\\% confidence interval, 1.04???2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2\\% in the APOE*2 carriers compared with 27.8\\% and 24.8\\% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06???2.05). Conclusion(s) This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.},\n\tnumber = {6},\n\tjournal = {Fertility and Sterility},\n\tauthor = {Gamundi-Segura, Silvia and Torres-Perez, Elena and Sanz-Paris, Alejandro and Arbones-Mainar, Jose M.},\n\tmonth = mar,\n\tyear = {2016},\n\tpmid = {26952784},\n\tnote = {Publisher: Elsevier},\n\tpages = {1554--1560.e1},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/6HCKQI5J/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Objective To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. Design Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. locations. Setting Not applicable. Patient(s) Women without miscarriages (controls) and women who miscarried at least once (cases). Intervention(s) None. Main Outcome Measure(s) A group of women (n = 1,372) successfully followed for 25??years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. Result(s) In white women followed up for 25??years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95% confidence interval, 1.04???2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2% in the APOE*2 carriers compared with 27.8% and 24.8% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06???2.05). Conclusion(s) This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.sciencedirect.com/science/article/pii/S0261561416000893\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016', 'http://www.sciencedirect.com/science/article/pii/S0261561416000893', event);\">\n    Application of the new ESPEN definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Sanz-París, A.; Gómez-Candela, C.; Martín-Palmero, Á.; García-Almeida, J. M.; Burgos-Pelaez, R.; Matía-Martin, P.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Clinical Nutrition</i>, 35(6): 1564–1567.  2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.sciencedirect.com/science/article/pii/S0261561416000893\"\n     onclick=\"log_download('sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016', 'http://www.sciencedirect.com/science/article/pii/S0261561416000893', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Application of the new ESPEN definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view\"\n     onclick=\"log_download('sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016', 'https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Application of the new ESPEN definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.clnu.2016.02.018\"\n     onclick=\"log_download('sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016', 'http://doi.org/10.1016/j.clnu.2016.02.018', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('sanzpars-gmezcandela-martnpalmero-garcaalmeida-burgospelaez-matamartin-arbonesmainar-applicationofthenewespendefinitionofmalnutritioningeriatricdiabeticpatientsduringhospitalizationamulticentricstudy-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Sanz-Paris2016,\n\ttitle = {Application of the new {ESPEN} definition of malnutrition in geriatric diabetic patients during hospitalization: a multicentric study},\n\tvolume = {35},\n\tcopyright = {All rights reserved},\n\tissn = {02615614},\n\turl = {http://www.sciencedirect.com/science/article/pii/S0261561416000893},\n\tdoi = {10.1016/j.clnu.2016.02.018},\n\tabstract = {BACKGROUND \\&amp; AIMS The European Society for Clinical Nutrition and Metabolism (ESPEN) recently provided new diagnosis criteria of malnutrition and called to confirm those criteria in specific populations⁠⁠. The aims of our study were 1) to determine the prevalence of malnutrition according to the new ESPEN definition in elder hospitalized diabetic patients, and 2) to evaluate whether this new diagnosis of malnutrition predicted clinical outcomes in these patients. METHODS 1014 hospitalized diabetic patients (≥65 years) from 35 hospitals in Spain were screened for being at risk of malnutrition using the short version of the Mini Nutritional Assessment. Subsequently, at risk individuals were considered malnourished if they met at least one of the two options: 1) body mass index (BMI) {\\textless}18.5 kg/m2, or 2) unintentional weight loss {\\textgreater}5\\% of their body weight with reduced BMI ({\\textless}20 kg/m2 in subjects younger than 70 years or {\\textless}22 kg/m2 in subjects older than 70 years)⁠ RESULTS The new ESPEN definition, with MNA-SF as initial screening, identified 68 malnourished geriatric individuals with diabetes (6.73\\% of the cohort). Additionally, malnutrition lengthened the hospital stay, increased 2.7 times the odds of dying in hospital, and decreased to one third the odds of being discharged home. CONCLUSIONS Our study confirms that the new ESPEN definition for the diagnosis of malnutrition is a reliable tool that is capable of predicting clinical outcomes in a large population of elder hospitalized individuals with diabetes.},\n\tnumber = {6},\n\tjournal = {Clinical Nutrition},\n\tauthor = {Sanz-París, Alejandro and Gómez-Candela, Carmen and Martín-Palmero, Ángela and García-Almeida, José M. and Burgos-Pelaez, Rosa and Matía-Martin, Pilar and Arbones-Mainar, Jose M.},\n\tyear = {2016},\n\tpages = {1564--1567},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/TYHASBLS/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND & AIMS The European Society for Clinical Nutrition and Metabolism (ESPEN) recently provided new diagnosis criteria of malnutrition and called to confirm those criteria in specific populations⁠⁠. The aims of our study were 1) to determine the prevalence of malnutrition according to the new ESPEN definition in elder hospitalized diabetic patients, and 2) to evaluate whether this new diagnosis of malnutrition predicted clinical outcomes in these patients. METHODS 1014 hospitalized diabetic patients (≥65 years) from 35 hospitals in Spain were screened for being at risk of malnutrition using the short version of the Mini Nutritional Assessment. Subsequently, at risk individuals were considered malnourished if they met at least one of the two options: 1) body mass index (BMI) \\textless18.5 kg/m2, or 2) unintentional weight loss \\textgreater5% of their body weight with reduced BMI (\\textless20 kg/m2 in subjects younger than 70 years or \\textless22 kg/m2 in subjects older than 70 years)⁠ RESULTS The new ESPEN definition, with MNA-SF as initial screening, identified 68 malnourished geriatric individuals with diabetes (6.73% of the cohort). Additionally, malnutrition lengthened the hospital stay, increased 2.7 times the odds of dying in hospital, and decreased to one third the odds of being discharged home. CONCLUSIONS Our study confirms that the new ESPEN definition for the diagnosis of malnutrition is a reliable tool that is capable of predicting clinical outcomes in a large population of elder hospitalized individuals with diabetes.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.sciencedirect.com/science/article/pii/S0021915015302240\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016', 'http://www.sciencedirect.com/science/article/pii/S0021915015302240', event);\">\n    Apolipoprotein E4 association with metabolic syndrome depends on body fatness.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Torres-Perez, E.; Ledesma, M.; Garcia-Sobreviela, M. P.; Leon-Latre, M.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Atherosclerosis</i>, 245: 35–42. February 2016.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.sciencedirect.com/science/article/pii/S0021915015302240\"\n     onclick=\"log_download('torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016', 'http://www.sciencedirect.com/science/article/pii/S0021915015302240', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Apolipoprotein E4 association with metabolic syndrome depends on body fatness [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view\"\n     onclick=\"log_download('torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016', 'https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Apolipoprotein E4 association with metabolic syndrome depends on body fatness [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1016/j.atherosclerosis.2015.11.029\"\n     onclick=\"log_download('torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016', 'http://doi.org/10.1016/j.atherosclerosis.2015.11.029', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('torresperez-ledesma-garciasobreviela-leonlatre-arbonesmainar-apolipoproteine4associationwithmetabolicsyndromedependsonbodyfatness-2016')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Torres-Perez2016,\n\ttitle = {Apolipoprotein {E4} association with metabolic syndrome depends on body fatness},\n\tvolume = {245},\n\tcopyright = {All rights reserved},\n\tissn = {00219150},\n\turl = {http://www.sciencedirect.com/science/article/pii/S0021915015302240},\n\tdoi = {10.1016/j.atherosclerosis.2015.11.029},\n\tabstract = {BACKGROUND AND AIMS The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness. METHODS \\&amp; RESULTS We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95\\% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95\\% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95\\% CI, 1.07-1.55). CONCLUSIONS Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual&#x27;s APOE genotype might help identify at-risk subjects for preventive intervention.},\n\turldate = {2015-12-18},\n\tjournal = {Atherosclerosis},\n\tauthor = {Torres-Perez, Elena and Ledesma, Marta and Garcia-Sobreviela, Maria Pilar and Leon-Latre, Montserrat and Arbones-Mainar, Jose M.},\n\tmonth = feb,\n\tyear = {2016},\n\tpages = {35--42},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/MFL4JXIQ/file/view}\n}\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND AND AIMS The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness. METHODS & RESULTS We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95% CI, 1.07-1.55). CONCLUSIONS Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2015\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2015')\"\n      onkeypress=\"toggleGroup('group_2015')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2015</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.cardiab.com/content/14/1/40\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015', 'http://www.cardiab.com/content/14/1/40', event);\">\n    The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Torres-Perez, E.; Valero, M.; Garcia-Rodriguez, B.; Gonzalez-Irazabal, Y.; Calmarza, P.; Calvo-Ruata, L.; Ortega, C.; Garcia-Sobreviela, M.; Sanz-Paris, A.; Artigas, J.; Lagos, J.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Cardiovascular Diabetology</i>, 14(1): 40.  2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.cardiab.com/content/14/1/40\"\n     onclick=\"log_download('torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015', 'http://www.cardiab.com/content/14/1/40', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1186/s12933-015-0203-6\"\n     onclick=\"log_download('torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015', 'http://doi.org/10.1186/s12933-015-0203-6', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('torresperez-valero-garciarodriguez-gonzalezirazabal-calmarza-calvoruata-ortega-garciasobreviela-etal-thefatexpandabilityfateprojectbiomarkerstodeterminethelimitofexpansionandthecomplicationsofobesity-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Torres-Perez2015,\n\ttitle = {The {FAT} expandability ({FATe}) {Project}: {Biomarkers} to determine the limit of expansion and the complications of obesity},\n\tvolume = {14},\n\tcopyright = {All rights reserved},\n\tissn = {1475-2840},\n\turl = {http://www.cardiab.com/content/14/1/40},\n\tdoi = {10.1186/s12933-015-0203-6},\n\tabstract = {BACKGROUND:Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.METHODS/DESIGN:FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers&#x27; predictive performance.DISCUSSION:The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.},\n\tnumber = {1},\n\tjournal = {Cardiovascular Diabetology},\n\tauthor = {Torres-Perez, Elena and Valero, Monica and Garcia-Rodriguez, Beatriz and Gonzalez-Irazabal, Yolanda and Calmarza, Pilar and Calvo-Ruata, Luisa and Ortega, Carmen and Garcia-Sobreviela, Maria and Sanz-Paris, Alejandro and Artigas, Jose and Lagos, Javier and Arbones-Mainar, Jose},\n\tyear = {2015},\n\tpages = {40},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND:Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells.METHODS/DESIGN:FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance.DISCUSSION:The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25686566\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25686566', event);\">\n    Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Gamundi-Segura, S.; Serna, J.; Oehninger, S.; Horcajadas, J. A.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Physiology and Biochemistry</i>. February 2015.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/25686566\"\n     onclick=\"log_download('gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015', 'http://www.ncbi.nlm.nih.gov/pubmed/25686566', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view\"\n     onclick=\"log_download('gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015', 'https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1007/s13105-015-0393-0\"\n     onclick=\"log_download('gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015', 'http://doi.org/10.1007/s13105-015-0393-0', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('gamundisegura-serna-oehninger-horcajadas-arbonesmainar-effectsofadipocytesecretedfactorsondecidualizedendometrialcellsmodulationofendometrialreceptivityinvitro-2015')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Gamundi-Segura2015,\n\ttitle = {Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro},\n\tcopyright = {All rights reserved},\n\tissn = {18778755},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/25686566},\n\tdoi = {10.1007/s13105-015-0393-0},\n\tabstract = {Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.},\n\turldate = {2015-02-18},\n\tjournal = {Journal of Physiology and Biochemistry},\n\tauthor = {Gamundi-Segura, Silvia and Serna, Jose and Oehninger, Sergio and Horcajadas, Jose A. and Arbones-Mainar, Jose M.},\n\tmonth = feb,\n\tyear = {2015},\n\tpmid = {25686566},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/8UAGFWPE/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2014\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2014')\"\n      onkeypress=\"toggleGroup('group_2014')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2014</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/24812087\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014', 'http://www.ncbi.nlm.nih.gov/pubmed/24812087', event);\">\n    Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Perez-Diaz, S.; Johnson, L. A.; DeKroon, R. M.; Moreno-Navarrete, J. M.; Alzate, O.; Fernandez-Real, J. M.; Maeda, N.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M.</a>\n</span>\n\n  \n\n</span>\n\n  <i>FASEB journal</i>, 28: 1–11. May 2014.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.ncbi.nlm.nih.gov/pubmed/24812087\"\n     onclick=\"log_download('perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014', 'http://www.ncbi.nlm.nih.gov/pubmed/24812087', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability. [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n  <a href=\"https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view\"\n     onclick=\"log_download('perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014', 'https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability. [link]\"\n       title=\" paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\"> paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1096/fj.14-251165\"\n     onclick=\"log_download('perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014', 'http://doi.org/10.1096/fj.14-251165', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('perezdiaz-johnson-dekroon-morenonavarrete-alzate-fernandezreal-maeda-arbonesmainar-polymeraseiandtranscriptreleasefactorptrfregulatesadipocytedifferentiationanddeterminesadiposetissueexpandability-2014')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Perez-Diaz2014b,\n\ttitle = {Polymerase {I} and transcript release factor ({PTRF}) regulates adipocyte differentiation and determines adipose tissue expandability.},\n\tvolume = {28},\n\tcopyright = {All rights reserved},\n\tissn = {1530-6860},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/24812087},\n\tdoi = {10.1096/fj.14-251165},\n\tabstract = {Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management.-Perez-Diaz, S., Johnson, L. A., DeKroon, R. M., Moreno-Navarrete, J. M., Alzate, O., Fernandez-Real, J. M., Maeda, N., Arbones-Mainar, J. M. Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.},\n\turldate = {2014-05-15},\n\tjournal = {FASEB journal},\n\tauthor = {Perez-Diaz, Sergio and Johnson, Lance A. and DeKroon, Robert M. and Moreno-Navarrete, Jose M. and Alzate, Oscar and Fernandez-Real, Jose M. and Maeda, Nobuyo and Arbones-Mainar, Jose M.},\n\tmonth = may,\n\tyear = {2014},\n\tpmid = {24812087},\n\tpages = {1--11},\n\turl_paper={https://api.zotero.org/users/9838054/publications/items/74DBY7DY/file/view}\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Impaired adipogenesis renders an adipose tissue unable to expand, leading to lipotoxicity and conditions such as diabetes and cardiovascular disease. While factors important for adipogenesis have been studied extensively, those that set the limits of adipose tissue expansion remain undetermined. Feeding a Western-type diet to apolipoprotein E2 knock-in mice, a model of metabolic syndrome, produced 3 groups of equally obese mice: mice with normal glucose tolerance, hyperinsulinemic yet glucose-tolerant mice, and prediabetic mice with impaired glucose tolerance and reduced circulating insulin. Using proteomics, we compared subcutaneous adipose tissues from mice in these groups and found that the expression of PTRF (polymerase I and transcript release factor) associated selectively with their glucose tolerance status. Lentiviral and pharmacologically overexpressed PTRF, whose function is critical for caveola formation, compromised adipocyte differentiation of cultured 3T3-L1cells. In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. Furthermore, a negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. PTRF is associated with limited adipose tissue expansion underpinning the key role of caveolae in adipocyte regulation. Furthermore, PTRF may be a suitable adipocyte marker for predicting pathological obesity and inform clinical management.-Perez-Diaz, S., Johnson, L. A., DeKroon, R. M., Moreno-Navarrete, J. M., Alzate, O., Fernandez-Real, J. M., Maeda, N., Arbones-Mainar, J. M. Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&amp;tool=pmcentrez&amp;rendertype=abstract\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014', 'http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&amp;tool=pmcentrez&amp;rendertype=abstract', event);\">\n    The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Tejedor, M T.; Garcia-Sobreviela, M. P.; Ledesma, M.;  and <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M</a>\n</span>\n\n  \n\n</span>\n\n  <i>PloS one</i>, 9(9): e108605. January 2014.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&amp;tool=pmcentrez&amp;rendertype=abstract\"\n     onclick=\"log_download('tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014', 'http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&amp;tool=pmcentrez&amp;rendertype=abstract', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men. [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.1371/journal.pone.0108605\"\n     onclick=\"log_download('tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014', 'http://doi.org/10.1371/journal.pone.0108605', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('tejedor-garciasobreviela-ledesma-arbonesmainar-theapolipoproteinepolymorphismrs7412associateswithbodyfatnessindependentlyofplasmalipidsinmiddleagedmen-2014')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Tejedor2014,\n\ttitle = {The {Apolipoprotein} {E} {Polymorphism} rs7412 {Associates} with {Body} {Fatness} {Independently} of {Plasma} {Lipids} in {Middle} {Aged} {Men}.},\n\tvolume = {9},\n\tcopyright = {All rights reserved},\n\tissn = {1932-6203},\n\turl = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4182517&amp;tool=pmcentrez&amp;rendertype=abstract},\n\tdoi = {10.1371/journal.pone.0108605},\n\tabstract = {BACKGROUND: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.\n\nMETHODS: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.\n\nRESULTS: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI{\\textgreater}30) for individuals carrying the APOε2 allele, present in 14\\% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95\\% CI: 1.01-1.59).\n\nCONCLUSIONS: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.},\n\tnumber = {9},\n\turldate = {2014-11-11},\n\tjournal = {PloS one},\n\tauthor = {Tejedor, M Teresa and Garcia-Sobreviela, Maria Pilar and Ledesma, Marta and Arbones-Mainar, Jose M},\n\tmonth = jan,\n\tyear = {2014},\n\tpmid = {25268647},\n\tpages = {e108605},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  BACKGROUND: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined. METHODS: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease. RESULTS: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI\\textgreater30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01-1.59). CONCLUSIONS: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2011\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2011')\"\n      onkeypress=\"toggleGroup('group_2011')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2011</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  <a href=\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&amp;tool=pmcentrez&amp;rendertype=abstract\"\n     onclick=\"return trackOutboundLink('publications', 'click', 'johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011', 'http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&amp;tool=pmcentrez&amp;rendertype=abstract', event);\">\n    Apolipoprotein E4 Exaggerates Diabetic Dyslipidemia and Atherosclerosis in Mice Lacking the LDL Receptor.\n  </a>\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Johnson, L. A; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J. M</a>; Fox, R. G; Pendse, A. A; Altenburg, M. K; Kim, H.;  and Maeda, N.\n</span>\n\n  \n\n</span>\n\n  <i>Diabetes</i>, 60(9): 2285–94. September 2011.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n  <a href=\"http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&amp;tool=pmcentrez&amp;rendertype=abstract\"\n     onclick=\"log_download('johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011', 'http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&amp;tool=pmcentrez&amp;rendertype=abstract', event.ctrlKey, event)\">\n    <img src=\"//bibbase.org/img/filetypes/link.svg\"\n\t     alt=\"Apolipoprotein E4 Exaggerates Diabetic Dyslipidemia and Atherosclerosis in Mice Lacking the LDL Receptor. [link]\"\n       title=\"Paper\"\n\t     class=\"bibbase_icon\"\n         ><span class=\"bibbase_icon_text\">Paper</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"http://doi.org/10.2337/db11-0466\"\n     onclick=\"log_download('johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011', 'http://doi.org/10.2337/db11-0466', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('johnson-arbonesmainar-fox-pendse-altenburg-kim-maeda-apolipoproteine4exaggeratesdiabeticdyslipidemiaandatherosclerosisinmicelackingtheldlreceptor-2011')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{Johnson2011,\n\ttitle = {Apolipoprotein {E4} {Exaggerates} {Diabetic} {Dyslipidemia} and {Atherosclerosis} in {Mice} {Lacking} the {LDL} {Receptor}.},\n\tvolume = {60},\n\tcopyright = {All rights reserved},\n\tissn = {1939-327X},\n\turl = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3161311&amp;tool=pmcentrez&amp;rendertype=abstract},\n\tdoi = {10.2337/db11-0466},\n\tabstract = {OBJECTIVE We investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia-a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR(-/-)). RESULTS Diabetic E3LDLR(-/-) and E4LDLR(-/-) mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR(-/-) mice twice as much as in E3LDLR(-/-) mice. Diabetic E4LDLR(-/-) mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR(-/-) mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR(-/-) mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR(-/-) primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR(-/-) hepatocytes concomitant with a 60\\% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR(-/-) mice was accompanied by a dramatic increase in atherosclerosis. CONCLUSIONS ApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.},\n\tnumber = {9},\n\turldate = {2011-09-13},\n\tjournal = {Diabetes},\n\tauthor = {Johnson, Lance A and Arbones-Mainar, Jose M and Fox, Raymond G and Pendse, Avani A and Altenburg, Michael K and Kim, Hyung-Suk and Maeda, Nobuyo},\n\tmonth = sep,\n\tyear = {2011},\n\tpmid = {21810592},\n\tpages = {2285--94},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  OBJECTIVE We investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia-a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR(-/-)). RESULTS Diabetic E3LDLR(-/-) and E4LDLR(-/-) mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR(-/-) mice twice as much as in E3LDLR(-/-) mice. Diabetic E4LDLR(-/-) mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR(-/-) mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR(-/-) mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR(-/-) primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR(-/-) hepatocytes concomitant with a 60% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR(-/-) mice was accompanied by a dramatic increase in atherosclerosis. CONCLUSIONS ApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2010\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2010')\"\n      onkeypress=\"toggleGroup('group_2010')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2010</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"deroos-arbonesmainar-gutirrez-theeffectsofoliveoilsonhepaticlipidmetabolismandantioxidantdefensemechanismsinsightsfromproteomicsstudies-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  The Effects of Olive Oils on Hepatic Lipid Metabolism and Antioxidant Defense Mechanisms: Insights from Proteomics Studies.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  De Roos, B.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>;  and Gutiérrez, G.\n</span>\n\n  \n\n</span>\n\n   2010.\n  <span class=\"note\">Publication Title: Olives and Olive Oil in Health and Disease Prevention</span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1016/B978-0-12-374420-3.00095-4\"\n     onclick=\"log_download('deroos-arbonesmainar-gutirrez-theeffectsofoliveoilsonhepaticlipidmetabolismandantioxidantdefensemechanismsinsightsfromproteomicsstudies-2010', 'http://doi.org/10.1016/B978-0-12-374420-3.00095-4', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/deroos-arbonesmainar-gutirrez-theeffectsofoliveoilsonhepaticlipidmetabolismandantioxidantdefensemechanismsinsightsfromproteomicsstudies-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('deroos-arbonesmainar-gutirrez-theeffectsofoliveoilsonhepaticlipidmetabolismandantioxidantdefensemechanismsinsightsfromproteomicsstudies-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@book{de_roos_effects_2010,\n\ttitle = {The {Effects} of {Olive} {Oils} on {Hepatic} {Lipid} {Metabolism} and {Antioxidant} {Defense} {Mechanisms}: {Insights} from {Proteomics} {Studies}},\n\tcopyright = {All rights reserved},\n\tisbn = {978-0-12-374420-3},\n\tabstract = {Olive oil is a natural juice of the olive fruit, and it is a major fat source in the Mediterranean diet. Although this diet is associated with a lower rate of coronary heart disease (CHD), as well as a reduction in all-cause mortality, data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. The Mediterranean diet might protect against coronary heart disease through improvement of the lipoprotein profile, improvement of the postprandial pro-thrombotic profile, lowering of blood pressure, and an improvement in insulin sensitivity both in healthy and in type 2 diabetic patients. These potential beneficial effects of olive oil suggest that its consumption affects hepatic lipid and glucose metabolism. Effects of olive oil on health may be due to both its high content of mono-unsaturated fatty acids or alternatively, due to its polar, minor components, which are rich in antioxidant phenolics. As natural dietary antioxidants, these phenolic compounds may protect the organism against damage caused by oxidant agents like active oxygen species and free radicals. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved.},\n\tauthor = {De Roos, B. and Arbones-Mainar, J.M. and Gutiérrez, G.R.},\n\tyear = {2010},\n\tdoi = {10.1016/B978-0-12-374420-3.00095-4},\n\tnote = {Publication Title: Olives and Olive Oil in Health and Disease Prevention},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Olive oil is a natural juice of the olive fruit, and it is a major fat source in the Mediterranean diet. Although this diet is associated with a lower rate of coronary heart disease (CHD), as well as a reduction in all-cause mortality, data concerning olive oil consumption and primary end points for cardiovascular disease are scarce. The Mediterranean diet might protect against coronary heart disease through improvement of the lipoprotein profile, improvement of the postprandial pro-thrombotic profile, lowering of blood pressure, and an improvement in insulin sensitivity both in healthy and in type 2 diabetic patients. These potential beneficial effects of olive oil suggest that its consumption affects hepatic lipid and glucose metabolism. Effects of olive oil on health may be due to both its high content of mono-unsaturated fatty acids or alternatively, due to its polar, minor components, which are rich in antioxidant phenolics. As natural dietary antioxidants, these phenolic compounds may protect the organism against damage caused by oxidant agents like active oxygen species and free radicals. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"arbonesmainar-johnson-altenburg-kim-maeda-impairedadipogenicresponsetothiazolidinedionesinmiceexpressinghumanapolipoproteine4-2010\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Impaired adipogenic response to thiazolidinediones in mice expressing human apolipoproteinE4.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Johnson, L.; Altenburg, M.; Kim, H.;  and Maeda, N.\n</span>\n\n  \n\n</span>\n\n  <i>FASEB Journal</i>, 24(10).  2010.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1096/fj.10-159517\"\n     onclick=\"log_download('arbonesmainar-johnson-altenburg-kim-maeda-impairedadipogenicresponsetothiazolidinedionesinmiceexpressinghumanapolipoproteine4-2010', 'http://doi.org/10.1096/fj.10-159517', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/arbonesmainar-johnson-altenburg-kim-maeda-impairedadipogenicresponsetothiazolidinedionesinmiceexpressinghumanapolipoproteine4-2010\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('arbonesmainar-johnson-altenburg-kim-maeda-impairedadipogenicresponsetothiazolidinedionesinmiceexpressinghumanapolipoproteine4-2010')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{arbones-mainar_impaired_2010,\n\ttitle = {Impaired adipogenic response to thiazolidinediones in mice expressing human {apolipoproteinE4}},\n\tvolume = {24},\n\tcopyright = {All rights reserved},\n\tissn = {15306860},\n\tdoi = {10.1096/fj.10-159517},\n\tabstract = {Thiazolidinediones (TZDs) are insulin sensitizers used to treat patients with insulin resistance. To assess potential gene-drug interactions, mice expressing human apolipoprotein E3 or E4 (APOE3 or APOE4) were fed a Western-type high-fat diet for 12 wk, at which time they developed similarly impaired glucose tolerance. Supplementing the diet with rosiglitazone (1.5 mg/g body weight) for an additional 4 wk improved plasma lipid profiles in both APOE3 and APOE4 mice. However, glucose tolerance improved only in APOE3 mice. Induction of adipogenesis and lipogenesis was severely blunted in adipose tissues, but not in the livers, of APOE4 mice. Consequently, lipids were channeled to the liver, causing marked steatosis in these mice. Impaired glucose tolerance was not a prerequisite for this adverse effect, and long-term treatment with rosiglitazone altered liver enzymes and caused hepatic fibrosis in APOE4 mice. Finally, TZDs failed to stimulate PPARγ activation and adipocyte differentiation in preadipocytes and embryonic fibroblasts isolated from APOE4 mice compared to those from APOE3 mice. We conclude that the effects of TZDs are APOE isoform dependent, and that the metabolic damage observed in APOE4 mice is rooted in an impaired activation of the adipogenic program in the adipose tissues expressing APOE4. © FASEB.},\n\tnumber = {10},\n\tjournal = {FASEB Journal},\n\tauthor = {Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Kim, H.-S. and Maeda, N.},\n\tyear = {2010},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Thiazolidinediones (TZDs) are insulin sensitizers used to treat patients with insulin resistance. To assess potential gene-drug interactions, mice expressing human apolipoprotein E3 or E4 (APOE3 or APOE4) were fed a Western-type high-fat diet for 12 wk, at which time they developed similarly impaired glucose tolerance. Supplementing the diet with rosiglitazone (1.5 mg/g body weight) for an additional 4 wk improved plasma lipid profiles in both APOE3 and APOE4 mice. However, glucose tolerance improved only in APOE3 mice. Induction of adipogenesis and lipogenesis was severely blunted in adipose tissues, but not in the livers, of APOE4 mice. Consequently, lipids were channeled to the liver, causing marked steatosis in these mice. Impaired glucose tolerance was not a prerequisite for this adverse effect, and long-term treatment with rosiglitazone altered liver enzymes and caused hepatic fibrosis in APOE4 mice. Finally, TZDs failed to stimulate PPARγ activation and adipocyte differentiation in preadipocytes and embryonic fibroblasts isolated from APOE4 mice compared to those from APOE3 mice. We conclude that the effects of TZDs are APOE isoform dependent, and that the metabolic damage observed in APOE4 mice is rooted in an impaired activation of the adipogenic program in the adipose tissues expressing APOE4. © FASEB.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2009\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2009')\"\n      onkeypress=\"toggleGroup('group_2009')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2009</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"pendse-arbonesmainar-johnson-altenburg-maeda-apolipoproteineknockoutandknockinmiceatherosclerosismetabolicsyndromeandbeyond-2009\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Apolipoprotein E knock-out and knock-in mice: Atherosclerosis, metabolic syndrome, and beyond.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Pendse, A.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Johnson, L.; Altenburg, M.;  and Maeda, N.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Lipid Research</i>, 50(SUPPL.).  2009.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1194/jlr.R800070-JLR200\"\n     onclick=\"log_download('pendse-arbonesmainar-johnson-altenburg-maeda-apolipoproteineknockoutandknockinmiceatherosclerosismetabolicsyndromeandbeyond-2009', 'http://doi.org/10.1194/jlr.R800070-JLR200', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/pendse-arbonesmainar-johnson-altenburg-maeda-apolipoproteineknockoutandknockinmiceatherosclerosismetabolicsyndromeandbeyond-2009\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('pendse-arbonesmainar-johnson-altenburg-maeda-apolipoproteineknockoutandknockinmiceatherosclerosismetabolicsyndromeandbeyond-2009')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{pendse_apolipoprotein_2009,\n\ttitle = {Apolipoprotein {E} knock-out and knock-in mice: {Atherosclerosis}, metabolic syndrome, and beyond},\n\tvolume = {50},\n\tcopyright = {All rights reserved},\n\tissn = {00222275},\n\tdoi = {10.1194/jlr.R800070-JLR200},\n\tabstract = {Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to studymultiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases. Copyright ©2009 by the American Society for Biochemistry and Molecular Biology, Inc.},\n\tnumber = {SUPPL.},\n\tjournal = {Journal of Lipid Research},\n\tauthor = {Pendse, A.A. and Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Maeda, N.},\n\tyear = {2009},\n}\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to studymultiple facets of atherogenesis and to explore potential therapeutic interventions. In addition to its well-established role in lipoprotein metabolism, recent observations of reduced adiposity and improved glucose homeostasis in apoEKO mice suggest that apoE may also play a key role in energy metabolism in peripheral organs, including adipose tissue. Finally, along with apoEKO mice, knockin mice expressing human apoE isoforms in place of endogenous mouse apoE have provided insights into how quantitative and qualitative genetic alterations interact with the environment in the pathogenesis of complex human diseases. Copyright ©2009 by the American Society for Biochemistry and Molecular Biology, Inc.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2008\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2008')\"\n      onkeypress=\"toggleGroup('group_2008')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2008</span>\n      <span class=\"bibbase_group_count\">\n        \n        (3)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"arbonesmainar-johnson-altenburg-maeda-differentialmodulationofdietinducedobesityandadipocytefunctionalitybyhumanapolipoproteine3ande4inmice-2008\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Johnson, L.; Altenburg, M.;  and Maeda, N.\n</span>\n\n  \n\n</span>\n\n  <i>International Journal of Obesity</i>, 32(10).  2008.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1038/ijo.2008.143\"\n     onclick=\"log_download('arbonesmainar-johnson-altenburg-maeda-differentialmodulationofdietinducedobesityandadipocytefunctionalitybyhumanapolipoproteine3ande4inmice-2008', 'http://doi.org/10.1038/ijo.2008.143', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/arbonesmainar-johnson-altenburg-maeda-differentialmodulationofdietinducedobesityandadipocytefunctionalitybyhumanapolipoproteine3ande4inmice-2008\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('arbonesmainar-johnson-altenburg-maeda-differentialmodulationofdietinducedobesityandadipocytefunctionalitybyhumanapolipoproteine3ande4inmice-2008')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{arbones-mainar_differential_2008,\n\ttitle = {Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein {E3} and {E4} in mice},\n\tvolume = {32},\n\tcopyright = {All rights reserved},\n\tissn = {03070565},\n\tdoi = {10.1038/ijo.2008.143},\n\tabstract = {Objective: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly expressed in adipose tissues. Studies have shown that human APOE*4 is associated with a lower body mass index but with a greater risk of coronary heart disease compared with other APOE alleles. To define the isoform-specific role of apoE in regulating the expandability and functionality of adipose tissues, we investigated the effects of diet-induced obesity in mice whose endogenous Apoe gene has been replaced by either the human APOE*3 or APOE*4 allele. Results: After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed impaired tolerance to glucose and fat overload compared with APOE3 mice. Subcutaneous fat tissues in APOE4 and APOE3 mice after high fat feeding were not different. In contrast, although epididymal fat tissues in APOE4 mice gained 30\\% less weight during the high fat feeding than in APOE3 mice, they showed impaired insulin-stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were larger in size than APOE3 adipocytes, and expressed reduced levels of mRNA for peroxisome proliferator-activated receptor γ2 and adiponectin, important markers of adipocyte functionality. Adenoviral expression of apoE3 in apoE-null culture adipocytes induced adiponectin mRNA in a dose-dependent manner, but the induction was significantly blunted in cells overexpressing apoE4. However, in contrast to the apoE3-expressing cells, Glut1, but not Glut4, expression levels were positively correlated with increased apoE4 mRNA, suggesting that apoE4 expression in adipocyte interferes in insulin-sensing pathways. Conclusion: Dysfunctional epididymal adipose tissues contribute to the accelerated impairment of glucose tolerance in APOE4 mice fed a Western-type diet. Our results underscore the importance of functionality of individual fat depots rather than total fat mass as a determinant for metabolic disturbance during diet-induced obesity. © 2008 Macmillan Publishers Limited All rights reserved.},\n\tnumber = {10},\n\tjournal = {International Journal of Obesity},\n\tauthor = {Arbones-Mainar, J.M. and Johnson, L.A. and Altenburg, M.K. and Maeda, N.},\n\tyear = {2008},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Objective: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly expressed in adipose tissues. Studies have shown that human APOE*4 is associated with a lower body mass index but with a greater risk of coronary heart disease compared with other APOE alleles. To define the isoform-specific role of apoE in regulating the expandability and functionality of adipose tissues, we investigated the effects of diet-induced obesity in mice whose endogenous Apoe gene has been replaced by either the human APOE*3 or APOE*4 allele. Results: After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed impaired tolerance to glucose and fat overload compared with APOE3 mice. Subcutaneous fat tissues in APOE4 and APOE3 mice after high fat feeding were not different. In contrast, although epididymal fat tissues in APOE4 mice gained 30% less weight during the high fat feeding than in APOE3 mice, they showed impaired insulin-stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were larger in size than APOE3 adipocytes, and expressed reduced levels of mRNA for peroxisome proliferator-activated receptor γ2 and adiponectin, important markers of adipocyte functionality. Adenoviral expression of apoE3 in apoE-null culture adipocytes induced adiponectin mRNA in a dose-dependent manner, but the induction was significantly blunted in cells overexpressing apoE4. However, in contrast to the apoE3-expressing cells, Glut1, but not Glut4, expression levels were positively correlated with increased apoE4 mRNA, suggesting that apoE4 expression in adipocyte interferes in insulin-sensing pathways. Conclusion: Dysfunctional epididymal adipose tissues contribute to the accelerated impairment of glucose tolerance in APOE4 mice fed a Western-type diet. Our results underscore the importance of functionality of individual fat depots rather than total fat mass as a determinant for metabolic disturbance during diet-induced obesity. © 2008 Macmillan Publishers Limited All rights reserved.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"carnicer-guzman-acin-surra-navarro-arbonesmainar-arnal-morales-etal-geneticbackgroundinapolipoproteinaiandcystathioninesynthasedeficiency-2008\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Genetic background in apolipoprotein A-I and cystathionine β-synthase deficiency.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Carnicer, R.; Guzman, M.; Acin, S.; Surra, J.; Navarro, M.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Arnal, C.; Morales, R.;  and Osada, J.\n</span>\n\n  \n\n</span>\n\n  <i>Frontiers in Bioscience</i>, 13(13).  2008.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.2741/3071\"\n     onclick=\"log_download('carnicer-guzman-acin-surra-navarro-arbonesmainar-arnal-morales-etal-geneticbackgroundinapolipoproteinaiandcystathioninesynthasedeficiency-2008', 'http://doi.org/10.2741/3071', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/carnicer-guzman-acin-surra-navarro-arbonesmainar-arnal-morales-etal-geneticbackgroundinapolipoproteinaiandcystathioninesynthasedeficiency-2008\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('carnicer-guzman-acin-surra-navarro-arbonesmainar-arnal-morales-etal-geneticbackgroundinapolipoproteinaiandcystathioninesynthasedeficiency-2008')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{carnicer_genetic_2008,\n\ttitle = {Genetic background in apolipoprotein {A}-{I} and cystathionine β-synthase deficiency},\n\tvolume = {13},\n\tcopyright = {All rights reserved},\n\tissn = {10939946},\n\tdoi = {10.2741/3071},\n\tabstract = {Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.},\n\tnumber = {13},\n\tjournal = {Frontiers in Bioscience},\n\tauthor = {Carnicer, R. and Guzman, M.A. and Acin, S. and Surra, J.C. and Navarro, M.A. and Arbones-Mainar, J.M. and Arnal, C. and Morales, R. and Osada, J.},\n\tyear = {2008},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Double heterozygous mice lacking one allele of Cbs and Apoa1 develop hyperhomocysteinemia and hypoalphalipoproteinemia together with moderate hypertension. To study the influence of the genetic background into this specific phenotype, four groups of male mice were established: control and double heterozygous groups in C57BL/6J and in C57BL/6J x 129 backgrounds, respectively. Nitric oxide levels, systolic blood pressure, plasma lipid parameters, arylesterase activity and aorta histology were analyzed as well as oligonucleotide array hybridization of liver RNA. Results demonstrated that double heterozygous mice in C57BL/6J substrate had a milder phenotype showing lower increase in blood pressure compared to double heterozygous group in hybrid background. The severity of the phenotype in the latter group was associated with lower nitric oxide and arylesterase activity levels, and hyperplasia of the vascular media layer. Hepatic profiling of both genetic substrates showed profound differences in expression of contractile proteins that could explain these pathological findings. In summary, the phenotypic presentation of hypertension is associated with multiple processes from vascular bedside to liver as evidenced by nitric oxide production or paraoxonase levels.\n</div>\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"altenburg-arbonesmainar-johnson-wilder-maeda-humanldlreceptorenhancessequestrationofapoe4andvldlremnantsonthesurfaceofhepatocytesbutnottheirinternalizationinmice-2008\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Human LDL receptor enhances sequestration of apoE4 and VLDL remnants on the surface of hepatocytes but not their internalization in mice.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Altenburg, M.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Johnson, L.; Wilder, J.;  and Maeda, N.\n</span>\n\n  \n\n</span>\n\n  <i>Arteriosclerosis, Thrombosis, and Vascular Biology</i>, 28(6).  2008.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1161/ATVBAHA.108.164863\"\n     onclick=\"log_download('altenburg-arbonesmainar-johnson-wilder-maeda-humanldlreceptorenhancessequestrationofapoe4andvldlremnantsonthesurfaceofhepatocytesbutnottheirinternalizationinmice-2008', 'http://doi.org/10.1161/ATVBAHA.108.164863', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/altenburg-arbonesmainar-johnson-wilder-maeda-humanldlreceptorenhancessequestrationofapoe4andvldlremnantsonthesurfaceofhepatocytesbutnottheirinternalizationinmice-2008\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('altenburg-arbonesmainar-johnson-wilder-maeda-humanldlreceptorenhancessequestrationofapoe4andvldlremnantsonthesurfaceofhepatocytesbutnottheirinternalizationinmice-2008')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{altenburg_human_2008,\n\ttitle = {Human {LDL} receptor enhances sequestration of {apoE4} and {VLDL} remnants on the surface of hepatocytes but not their internalization in mice},\n\tvolume = {28},\n\tcopyright = {All rights reserved},\n\tissn = {10795642},\n\tdoi = {10.1161/ATVBAHA.108.164863},\n\tabstract = {Objective - In humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR). Methods and Results-Primary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-density lipoprotein (VLDL) remnants accumulated on the hepatocyte surface in apoE4 mice with high LDLR, but they were internalized poorly. In contrast, apoE2-GFP did not accumulate on the hepatocyte surface even when the LDLR expression was high, but apoE2 mice with high LDLR internalized the remnants avidly without sequestering them on the hepatocyte surface. Conclusions-The high affinity of apoE4 to the LDLR enhances VLDL sequestration on the hepatocyte surface but delays their internalization. This delay likely increases VLDL conversion to cholesterol-enriched remnants in apoE4 mice with high LDLR, and probably to LDL in humans with apoE4. © 2008 American Heart Association, Inc.},\n\tnumber = {6},\n\tjournal = {Arteriosclerosis, Thrombosis, and Vascular Biology},\n\tauthor = {Altenburg, M. and Arbones-Mainar, J. and Johnson, L. and Wilder, J. and Maeda, N.},\n\tyear = {2008},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  Objective - In humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR). Methods and Results-Primary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-density lipoprotein (VLDL) remnants accumulated on the hepatocyte surface in apoE4 mice with high LDLR, but they were internalized poorly. In contrast, apoE2-GFP did not accumulate on the hepatocyte surface even when the LDLR expression was high, but apoE2 mice with high LDLR internalized the remnants avidly without sequestering them on the hepatocyte surface. Conclusions-The high affinity of apoE4 to the LDLR enhances VLDL sequestration on the hepatocyte surface but delays their internalization. This delay likely increases VLDL conversion to cholesterol-enriched remnants in apoE4 mice with high LDLR, and probably to LDL in humans with apoE4. © 2008 American Heart Association, Inc.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2007\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2007')\"\n      onkeypress=\"toggleGroup('group_2007')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2007</span>\n      <span class=\"bibbase_group_count\">\n        \n        (2)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"carnicer-navarro-arbonesmainar-acin-guzman-surra-arnal-delasheras-etal-folicacidsupplementationdelaysatheroscleroticlesiondevelopmentinapoedeficientmice-2007\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Folic acid supplementation delays atherosclerotic lesion development in apoE-deficient mice.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Carnicer, R.; Navarro, M.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Acin, S.; Guzman, M.; Surra, J.; Arnal, C.; De Las Heras, M.; Blanco-Vaca, F.; Osada, J.;  and Antonia Vilaseca, M.\n</span>\n\n  \n\n</span>\n\n  <i>Clinica e Investigacion en Arteriosclerosis</i>, 19(2).  2007.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1016/S0214-9168(07)74181-5\"\n     onclick=\"log_download('carnicer-navarro-arbonesmainar-acin-guzman-surra-arnal-delasheras-etal-folicacidsupplementationdelaysatheroscleroticlesiondevelopmentinapoedeficientmice-2007', 'http://doi.org/10.1016/S0214-9168(07)74181-5', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/carnicer-navarro-arbonesmainar-acin-guzman-surra-arnal-delasheras-etal-folicacidsupplementationdelaysatheroscleroticlesiondevelopmentinapoedeficientmice-2007\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('carnicer-navarro-arbonesmainar-acin-guzman-surra-arnal-delasheras-etal-folicacidsupplementationdelaysatheroscleroticlesiondevelopmentinapoedeficientmice-2007')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{carnicer_folic_2007,\n\ttitle = {Folic acid supplementation delays atherosclerotic lesion development in {apoE}-deficient mice},\n\tvolume = {19},\n\tcopyright = {All rights reserved},\n\tissn = {15781879},\n\tdoi = {10.1016/S0214-9168(07)74181-5},\n\tnumber = {2},\n\tjournal = {Clinica e Investigacion en Arteriosclerosis},\n\tauthor = {Carnicer, R. and Navarro, M. and Arbones-Mainar, J.M. and Acin, S. and Guzman, M.A. and Surra, J.C. and Arnal, C. and De Las Heras, M. and Blanco-Vaca, F. and Osada, J. and Antonia Vilaseca, M.},\n\tyear = {2007},\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n  <div class=\"bibbase_paper\" id=\"arbonesmainar-ross-rucklidge-reid-duncan-arthur-horgan-navarro-etal-extravirginoliveoilsincreasehepaticfataccumulationandhepaticantioxidantproteinlevelsinapoetextrmmice-2007\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in APOE$^{\\textrm{-/-}}$mice.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Ross, K.; Rucklidge, G.; Reid, M.; Duncan, G.; Arthur, J.; Horgan, G.; Navarro, M.; Carnicer, R.; Arnal, C.; Osada, J.;  and De Roos, B.\n</span>\n\n  \n\n</span>\n\n  <i>Journal of Proteome Research</i>, 6(10).  2007.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1021/pr070321a\"\n     onclick=\"log_download('arbonesmainar-ross-rucklidge-reid-duncan-arthur-horgan-navarro-etal-extravirginoliveoilsincreasehepaticfataccumulationandhepaticantioxidantproteinlevelsinapoetextrmmice-2007', 'http://doi.org/10.1021/pr070321a', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/arbonesmainar-ross-rucklidge-reid-duncan-arthur-horgan-navarro-etal-extravirginoliveoilsincreasehepaticfataccumulationandhepaticantioxidantproteinlevelsinapoetextrmmice-2007\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('arbonesmainar-ross-rucklidge-reid-duncan-arthur-horgan-navarro-etal-extravirginoliveoilsincreasehepaticfataccumulationandhepaticantioxidantproteinlevelsinapoetextrmmice-2007')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{arbones-mainar_extra_2007,\n\ttitle = {Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in {APOE}$^{\\textrm{-/-}}$mice},\n\tvolume = {6},\n\tcopyright = {All rights reserved},\n\tissn = {15353893},\n\tdoi = {10.1021/pr070321a},\n\tabstract = {We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe -/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p  {\\textless}  0.05), though Picual olive oil significantly decreased plasma triglycerides (p  {\\textless}  0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our &quot;systems biology&quot; approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti-atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis. © 2007 American Chemical Society.},\n\tnumber = {10},\n\tjournal = {Journal of Proteome Research},\n\tauthor = {Arbones-Mainar, J.M. and Ross, K. and Rucklidge, G.J. and Reid, M. and Duncan, G. and Arthur, J.R. and Horgan, G.W. and Navarro, M.A. and Carnicer, R. and Arnal, C. and Osada, J. and De Roos, B.},\n\tyear = {2007},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe -/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p \\textless 0.05), though Picual olive oil significantly decreased plasma triglycerides (p \\textless 0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our \"systems biology\" approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti-atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis. © 2007 American Chemical Society.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2006\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2006')\"\n      onkeypress=\"toggleGroup('group_2006')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2006</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"sarria-surra-acin-carnicer-navarro-arbonesmainar-guillen-martinezgracia-etal-understandingtheroleofdietarycomponentsonatherosclerosisusinggeneticengineeredmousemodels-2006\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Understanding the role of dietary components on atherosclerosis using genetic engineered mouse models.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  Sarria, A.; Surra, J.; Acin, S.; Carnicer, R.; Navarro, M.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Guillen, N.; Martinez-Gracia, M.; Arnal, C.;  and Osada, J.\n</span>\n\n  \n\n</span>\n\n  <i>Frontiers in Bioscience</i>, 11(1 P.889-1198).  2006.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.2741/1852\"\n     onclick=\"log_download('sarria-surra-acin-carnicer-navarro-arbonesmainar-guillen-martinezgracia-etal-understandingtheroleofdietarycomponentsonatherosclerosisusinggeneticengineeredmousemodels-2006', 'http://doi.org/10.2741/1852', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/sarria-surra-acin-carnicer-navarro-arbonesmainar-guillen-martinezgracia-etal-understandingtheroleofdietarycomponentsonatherosclerosisusinggeneticengineeredmousemodels-2006\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n  &nbsp;\n  <a class=\"bibbase_abstract_link bibbase link\"\n     href=\"#\"\n     onclick=\"showAbstract(event); return false;\">\n    abstract <i class=\"fa fa-caret-down\"></i></a>\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('sarria-surra-acin-carnicer-navarro-arbonesmainar-guillen-martinezgracia-etal-understandingtheroleofdietarycomponentsonatherosclerosisusinggeneticengineeredmousemodels-2006')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{sarria_understanding_2006,\n\ttitle = {Understanding the role of dietary components on atherosclerosis using genetic engineered mouse models},\n\tvolume = {11},\n\tcopyright = {All rights reserved},\n\tissn = {10939946},\n\tdoi = {10.2741/1852},\n\tabstract = {The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoicing potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.},\n\tnumber = {1 P.889-1198},\n\tjournal = {Frontiers in Bioscience},\n\tauthor = {Sarria, A.J. and Surra, J.C. and Acin, S. and Carnicer, R. and Navarro, M.A. and Arbones-Mainar, J.M. and Guillen, N. and Martinez-Gracia, M.V. and Arnal, C. and Osada, J.},\n\tyear = {2006},\n}\n\n\n\n</pre>\n</div>\n\n\n<div class=\"well well-small bibbase\" data-type=\"abstract\"\n     style=\"display:none\">\n  The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoicing potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.\n</div>\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n  <div class=\"bibbase_group_whole\" id=\"group_2005\">\n    <div class=\"bibbase_group\"\n      onclick=\"toggleGroup('group_2005')\"\n      onkeypress=\"toggleGroup('group_2005')\"\n      tabindex=\"0\">\n      <i class=\"fa fa-angle-down bibbase_group_head_icon\"></i>&nbsp;\n      <span>2005</span>\n      <span class=\"bibbase_group_count\">\n        \n        (1)\n        \n      </span>\n    </div>\n    <div class=\"bibbase_group_body\">\n      \n  \n  <div class=\"bibbase_paper\" id=\"deroos-rucklidge-reid-ross-duncan-navarro-arbonesmainar-guzmangarcia-etal-divergentmechanismsofcis9trans11andtrans10cis12conjugatedlinoleicacidaffectinginsulinresistanceandinflammationinapolipoproteineknockoutmiceaproteomicsapproach-2005\">\n  <span class=\"bibbase_paper_titleauthoryear\">\n\n  \n  <span class=\"bibbase_paper_title\">\n  \n  \n  \n  Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: A proteomics approach.\n  \n  \n  \n</span>\n\n  <span class=\"bibbase_paper_author\">\n  De Roos, B.; Rucklidge, G.; Reid, M.; Ross, K.; Duncan, G.; Navarro, M.; <a class=\"bibbase author link\" href=\"http://adipofat.com/pubs-2\">Arbones-Mainar, J.</a>; Guzman-Garcia, M.; Osada, J.; Browne, J.; Loscher, C.;  and Roche, H.\n</span>\n\n  \n\n</span>\n\n  <i>FASEB Journal</i>, 19(12).  2005.\n  <span class=\"note\"></span>\n\n<span class=\"bibbase_note\"></span>\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content dontprint\">\n\n  \n\n  \n  <a href=\"http://doi.org/10.1096/fj.05-3953fje\"\n     onclick=\"log_download('deroos-rucklidge-reid-ross-duncan-navarro-arbonesmainar-guzmangarcia-etal-divergentmechanismsofcis9trans11andtrans10cis12conjugatedlinoleicacidaffectinginsulinresistanceandinflammationinapolipoproteineknockoutmiceaproteomicsapproach-2005', 'http://doi.org/10.1096/fj.05-3953fje', event.ctrlKey)\"\n     class=\"bibbase doi link\">\n    <span>doi</span></a>\n  &nbsp;\n  \n\n  \n  <a href=\"//bibbase.org/network/publication/deroos-rucklidge-reid-ross-duncan-navarro-arbonesmainar-guzmangarcia-etal-divergentmechanismsofcis9trans11andtrans10cis12conjugatedlinoleicacidaffectinginsulinresistanceandinflammationinapolipoproteineknockoutmiceaproteomicsapproach-2005\"\n     class=\"bibbase bibbase_page link\">link</a>\n  &nbsp;\n  \n\n  <a href=\"#\"\n     onclick=\"showBib(event); return false;\"\n     class=\"bibbase bibtex link\">bibtex\n    <i class=\"fa fa-caret-down\"></i></a>\n\n  \n\n  \n\n  <!-- <a class=\"bibbase read link hidden\" -->\n  <!--    href=\"javascript:toggleRead('deroos-rucklidge-reid-ross-duncan-navarro-arbonesmainar-guzmangarcia-etal-divergentmechanismsofcis9trans11andtrans10cis12conjugatedlinoleicacidaffectinginsulinresistanceandinflammationinapolipoproteineknockoutmiceaproteomicsapproach-2005')\" -->\n  <!--    title=\"Marking this paper as read adds it to your library on BibBase.\" -->\n  <!--    > -->\n  <!--   <i class=\"fa fa-check\"></i>&nbsp; -->\n  <!--   <span>mark as read</span> -->\n  <!-- </a> -->\n\n  &nbsp;\n  \n  \n\n</span>\n\n<div class=\"well well-small bibbase\" data-type=\"bibtex\"\n     style=\"display:none\">\n  <pre style=\"white-space: pre-wrap;\">@article{de_roos_divergent_2005,\n\ttitle = {Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein {E} knockout mice: {A} proteomics approach},\n\tvolume = {19},\n\tcopyright = {All rights reserved},\n\tissn = {08926638},\n\tdoi = {10.1096/fj.05-3953fje},\n\tnumber = {12},\n\tjournal = {FASEB Journal},\n\tauthor = {De Roos, B. and Rucklidge, G. and Reid, M. and Ross, K. and Duncan, G. and Navarro, M.A. and Arbones-Mainar, J.M. and Guzman-Garcia, M.A. and Osada, J. and Browne, J. and Loscher, C.E. and Roche, H.M.},\n\tyear = {2005},\n}\n\n\n\n</pre>\n</div>\n\n\n\n</div>\n\n\n\n\n\n    </div>\n  </div>\n\n\n\n\n  </div>\n\n\n  <!-- Modal -->\n\n  <!-- <iframe id=\"bibbase_network_frame\" -->\n  <!--         src=\"//bibbase.org/network/control\" -->\n  <!--         style=\"display: none;\"> -->\n  <!-- </iframe> -->\n\n</div>\n"}; document.write(bibbase_data.data);