@article{ handgraaf_prevention_2013,
  title = {Prevention of obesity and insulin resistance by estrogens requires {ERα} activation function-2 ({ERαAF}-2), whereas {ERαAF}-1 is dispensable},
  volume = {62},
  doi = {10.2337/db13-0282},
  abstract = {The beneficial metabolic actions of estrogen-based therapies are mainly mediated by estrogen receptor α (ERα), a nuclear receptor that regulates gene transcription through two activation functions (AFs): AF-1 and AF-2. Using mouse models deleted electively for ERαAF-1 (ERαAF-1°) or ERαAF-2 (ERαAF-2°), we determined their respective roles in the actions of estrogens on body composition and glucose homeostasis in response to either a normal diet or a high-fat diet (HFD). ERαAF-2° males and females developed accelerated weight gain, massive adiposity, severe insulin resistance, and glucose intolerance--quite reminiscent of the phenotype observed in mice deleted for the entire ERα protein (ERα(-/-)). In striking contrast, ERαAF-1° and wild-type (wt) mice shared a similar metabolic phenotype. Accordingly, 17β-estradiol administration regulated key metabolic genes in insulin-sensitive tissues and conferred a strong protection against HFD-induced metabolic disturbances in wt and ERαAF-1° ovariectomized mice, whereas these actions were totally abrogated in ERαAF-2° and ERα(-/-) mice. Thus, whereas both AFs have been previously shown to contribute to endometrial and breast cancer cell proliferation, the protective effect of estrogens against obesity and insulin resistance depends on ERαAF-2 but not ERαAF-1, thereby delineating new options for selective modulation of ERα.},
  language = {en},
  number = {12},
  journal = {Diabetes},
  author = {Handgraaf, Sandra and Riant, Elodie and Fabre, Aurélie and Waget, Aurélie and Burcelin, Rémy and Lière, Philippe and Krust, Andrée and Chambon, Pierre and Arnal, Jean-François and Gourdy, Pierre},
  month = {December},
  year = {2013},
  keywords = {Chambon},
  pages = {4098--4108}
}

{"_id":"qhAngdcDjsxNdEdXk","authorIDs":[],"author_short":["Handgraaf, S.","Riant, E.","Fabre, A.","Waget, A.","Burcelin, R.","Lière, P.","Krust, A.","Chambon, P.","Arnal, J.F.","Gourdy, P."],"bibbaseid":"handgraaf-riant-fabre-waget-burcelin-lire-krust-chambon-arnal-gourdy-preventionofobesityandinsulinresistancebyestrogensrequireseractivationfunction2eraf2whereaseraf1isdispensable-2013","bibdata":{"abstract":"The beneficial metabolic actions of estrogen-based therapies are mainly mediated by estrogen receptor α (ERα), a nuclear receptor that regulates gene transcription through two activation functions (AFs): AF-1 and AF-2. Using mouse models deleted electively for ERαAF-1 (ERαAF-1°) or ERαAF-2 (ERαAF-2°), we determined their respective roles in the actions of estrogens on body composition and glucose homeostasis in response to either a normal diet or a high-fat diet (HFD). ERαAF-2° males and females developed accelerated weight gain, massive adiposity, severe insulin resistance, and glucose intolerance--quite reminiscent of the phenotype observed in mice deleted for the entire ERα protein (ERα(-/-)). In striking contrast, ERαAF-1° and wild-type (wt) mice shared a similar metabolic phenotype. Accordingly, 17β-estradiol administration regulated key metabolic genes in insulin-sensitive tissues and conferred a strong protection against HFD-induced metabolic disturbances in wt and ERαAF-1° ovariectomized mice, whereas these actions were totally abrogated in ERαAF-2° and ERα(-/-) mice. Thus, whereas both AFs have been previously shown to contribute to endometrial and breast cancer cell proliferation, the protective effect of estrogens against obesity and insulin resistance depends on ERαAF-2 but not ERαAF-1, thereby delineating new options for selective modulation of ERα.","author":["Handgraaf, Sandra","Riant, Elodie","Fabre, Aurélie","Waget, Aurélie","Burcelin, Rémy","Lière, Philippe","Krust, Andrée","Chambon, Pierre","Arnal, Jean-François","Gourdy, Pierre"],"author_short":["Handgraaf, S.","Riant, E.","Fabre, A.","Waget, A.","Burcelin, R.","Lière, P.","Krust, A.","Chambon, P.","Arnal, J.F.","Gourdy, P."],"bibtex":"@article{ handgraaf_prevention_2013,\n title = {Prevention of obesity and insulin resistance by estrogens requires {ERα} activation function-2 ({ERαAF}-2), whereas {ERαAF}-1 is dispensable},\n volume = {62},\n doi = {10.2337/db13-0282},\n abstract = {The beneficial metabolic actions of estrogen-based therapies are mainly mediated by estrogen receptor α (ERα), a nuclear receptor that regulates gene transcription through two activation functions (AFs): AF-1 and AF-2. Using mouse models deleted electively for ERαAF-1 (ERαAF-1°) or ERαAF-2 (ERαAF-2°), we determined their respective roles in the actions of estrogens on body composition and glucose homeostasis in response to either a normal diet or a high-fat diet (HFD). ERαAF-2° males and females developed accelerated weight gain, massive adiposity, severe insulin resistance, and glucose intolerance--quite reminiscent of the phenotype observed in mice deleted for the entire ERα protein (ERα(-/-)). In striking contrast, ERαAF-1° and wild-type (wt) mice shared a similar metabolic phenotype. Accordingly, 17β-estradiol administration regulated key metabolic genes in insulin-sensitive tissues and conferred a strong protection against HFD-induced metabolic disturbances in wt and ERαAF-1° ovariectomized mice, whereas these actions were totally abrogated in ERαAF-2° and ERα(-/-) mice. Thus, whereas both AFs have been previously shown to contribute to endometrial and breast cancer cell proliferation, the protective effect of estrogens against obesity and insulin resistance depends on ERαAF-2 but not ERαAF-1, thereby delineating new options for selective modulation of ERα.},\n language = {en},\n number = {12},\n journal = {Diabetes},\n author = {Handgraaf, Sandra and Riant, Elodie and Fabre, Aurélie and Waget, Aurélie and Burcelin, Rémy and Lière, Philippe and Krust, Andrée and Chambon, Pierre and Arnal, Jean-François and Gourdy, Pierre},\n month = {December},\n year = {2013},\n keywords = {Chambon},\n pages = {4098--4108}\n}","bibtype":"article","doi":"10.2337/db13-0282","id":"handgraaf_prevention_2013","journal":"Diabetes","key":"handgraaf_prevention_2013","keywords":"Chambon","language":"en","month":"December","number":"12","pages":"4098--4108","title":"Prevention of obesity and insulin resistance by estrogens requires ERα activation function-2 (ERαAF-2), whereas ERαAF-1 is dispensable","type":"article","volume":"62","year":"2013","bibbaseid":"handgraaf-riant-fabre-waget-burcelin-lire-krust-chambon-arnal-gourdy-preventionofobesityandinsulinresistancebyestrogensrequireseractivationfunction2eraf2whereaseraf1isdispensable-2013","role":"author","urls":{},"keyword":["Chambon"],"downloads":0},"bibtype":"article","biburl":"https://copy.com/yJeTigu7fF3GMfay","creationDate":"2015-03-24T09:12:13.569Z","downloads":0,"keywords":["chambon"],"search_terms":["prevention","obesity","insulin","resistance","estrogens","requires","activation","function","whereas","dispensable","handgraaf","riant","fabre","waget","burcelin","lière","krust","chambon","arnal","gourdy"],"title":"Prevention of obesity and insulin resistance by estrogens requires ERα activation function-2 (ERαAF-2), whereas ERαAF-1 is dispensable","year":2013,"dataSources":["cQkDY6Drbg7NYDmKy"]}