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

• Published in: Molecular metabolism (Germany) Vol. 2; no. 3; pp. 227 - 242
• Main Authors: Davis, Kathryn E, D. Neinast, Michael, Sun, Kai, M. Skiles, William, D. Bills, Jessica, A. Zehr, Jordan, Zeve, Daniel, D. Hahner, Lisa, W. Cox, Derek, M. Gent, Lana, Xu, Yong, V. Wang, Zhao, A. Khan, Sohaib, Clegg, Deborah J
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.08.2013; Elsevier
• Subjects: Endocrinology & Metabolism; Estrogen receptor alpha (ERα); Fibrosis; Inflammation; Original; White adipose tissue (WAT); White adipose tissue (WAT); ERβ; white adipose tissue; brown adipose tissue; ERα; estrogen receptor beta; BAT; estrogen receptor alpha; Fibrosis; Estrogen receptor alpha (ERα); Inflammation; WAT; ERα, estrogen receptor alpha; WAT, white adipose tissue; ERβ, estrogen receptor beta; BAT, brown adipose tissue
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2013.05.006

Abstract Our data demonstrate that estrogens, estrogen receptor-α (ERα), and estrogen receptor-β (ERβ) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that αERKO mice have increased adipose tissue inflammation and fibrosis prior to obesity onset. Selective deletion of adipose tissue ERα in adult mice using a novel viral vector technology recapitulated the findings in the total body ERα null mice. Generation of a novel mouse model, lacking ERα specifically from adipocytes (AdipoERα), 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 ERα. Lastly, we determined the role of ERβ in regulating inflammation and fibrosis, by breeding the AdipoERα into the βERKO background and found that in the absence of adipocyte ERα, ERβ has a protective role. These data suggest that adipose tissue and adipocyte ERα protects against adiposity, inflammation, and fibrosis in both males and females.