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

Our data demonstrate that estrogens, estrogen receptor-alpha (ER alpha), and estrogen receptor-beta (ER beta) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that alpha ERK0 mice have increased adipose tissue inflammation and fibrosis prior to obesity onset. Selective deletion of adipose tissue ER alpha in adult mice using a novel viral vector technology recapitulated the findings in the total body ER alpha null mice. Generation of a novel mouse model, lacking ER alpha specifically from adipocytes (AdipoER alpha), 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 alpha. Lastly, we determined the role of ER beta in regulating inflammation and fibrosis, by breeding the AdipoER alpha into the beta ERK0 background and found that in the absence of adipocyte ER alpha, ER beta has a protective role. These data suggest that adipose tissue and adipocyte ER alpha protects against adiposity, inflammation, and fibrosis in both males and females. (C) 2013 Elsevier GmbH. Open access under CC BY-NC-ND license.