Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health. Lecoutre, S., Maqdasy, S., Rizo-Roca, D., Renzi, G., Vlassakev, I., Alaeddine, L. M., Higos, R., Jalkanen, J., Zhong, J., Zareifi, D. S., Frendo-Cumbo, S., Massier, L., Hodek, O., Juvany, M., Moritz, T., de Castro Barbosa, T., Omar-Hmeadi, M., López-Yus, M., Merabtene, F., Abatan, J. B., Marcelin, G., El Hachem, E., Rouault, C., Bergo, M. O., Petrus, P., Zierath, J. R., Clément, K., Krook, A., Mejhert, N., & Rydén, M. Nature Metabolism, July, 2024. Publisher: Nature Publishing Group![Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.
@article{lecoutre_reduced_2024,
title = {Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health},
copyright = {2024 The Author(s)},
issn = {2522-5812},
url = {https://www.nature.com/articles/s42255-024-01083-y},
doi = {10.1038/s42255-024-01083-y},
abstract = {Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.},
language = {en},
urldate = {2024-07-19},
journal = {Nature Metabolism},
author = {Lecoutre, Simon and Maqdasy, Salwan and Rizo-Roca, David and Renzi, Gianluca and Vlassakev, Ivan and Alaeddine, Lynn M. and Higos, Romane and Jalkanen, Jutta and Zhong, Jiawei and Zareifi, Danae S. and Frendo-Cumbo, Scott and Massier, Lucas and Hodek, Ondrej and Juvany, Marta and Moritz, Thomas and de Castro Barbosa, Thais and Omar-Hmeadi, Muhmmad and López-Yus, Marta and Merabtene, Fatiha and Abatan, Jimon Boniface and Marcelin, Geneviève and El Hachem, Elie-Julien and Rouault, Christine and Bergo, Martin O. and Petrus, Paul and Zierath, Juleen R. and Clément, Karine and Krook, Anna and Mejhert, Niklas and Rydén, Mikael},
month = jul,
year = {2024},
note = {Publisher: Nature Publishing Group},
keywords = {Fat metabolism, Obesity},
pages = {1--18},
}
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