The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis

摘要

Our data demonstrate that estrogens, estrogen receptor-@a (ER@a), and estrogen receptor-@b (ER@b) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that @aERKO mice have increased adipose tissue inflammation and fibrosis prior to obesity onset. Selective deletion of adipose tissue ER@a in adult mice using a novel viral vector technology recapitulated the findings in the total body ER@a null mice. Generation of a novel mouse model, lacking ER@a specifically from adipocytes (AdipoER@a), demonstrated increased markers of fibrosis and inflammation, especially in the males. Additionally, we found that the beneficial effects of estrogens on adipose tissue require adipocyte ER@a. Lastly, we determined the role of ER@b in regulating inflammation and fibrosis, by breeding the AdipoER@a into the @bERKO background and found that in the absence of adipocyte ER@a, ER@b has a protective role. These data suggest that adipose tissue and adipocyte ER@a protects against adiposity, inflammation, and fibrosis in both males and females.