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

Kathryn E. Davis, Michael D. Neinast, Kai Sun, William M. Skiles, Jessica D. Bills, Jordan A. Zehr, Daniel Zeve, Lisa D. Hahner, Derek W. Cox, Lana M. Gent, Yong Xu, Zhao V. Wang, Sohaib A. Khan, Deborah J. Clegg

Research output: Contribution to journalArticle

123 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)227-242
Number of pages16
JournalMolecular Metabolism
Volume2
Issue number3
DOIs
StatePublished - Aug 1 2013

Keywords

  • Estrogen receptor alpha (ERα)
  • Fibrosis
  • Inflammation
  • White adipose tissue (WAT)

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Davis, K. E., D. Neinast, M., Sun, K., M. Skiles, W., D. Bills, J., A. Zehr, J., Zeve, D., D. Hahner, L., W. Cox, D., M. Gent, L., Xu, Y., V. Wang, Z., A. Khan, S., & Clegg, D. J. (2013). The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Molecular Metabolism, 2(3), 227-242. https://doi.org/10.1016/j.molmet.2013.05.006