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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #307109
Title: The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis

Author
item DAVIS, KATHRYN - University Of Texas Southwestern Medical Center
item NEINAST, MICHAEL - University Of Texas Southwestern Medical Center
item SUN, KAI - University Of Texas Southwestern Medical Center
item SKILES, WILLIAM - University Of Texas Southwestern Medical Center
item BILLS, JESSICA - University Of Texas Southwestern Medical Center
item ZEHR, JORDAN - University Of Texas Southwestern Medical Center
item ZEVE, DANIEL - University Of Texas Southwestern Medical Center
item HAHNER, LISA - University Of Texas Southwestern Medical Center
item COX, DEREK - University Of Texas Southwestern Medical Center
item GENT, LANA - University Of Texas Southwestern Medical Center
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item WANG, ZHAO - University Of Texas Southwestern Medical Center
item KHAN, SOHAIB - University Of Cincinnati
item CLEGG, DEBORAH - University Of Texas Southwestern Medical Center

Submitted to: Molecular Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2013
Publication Date: 6/4/2013
Citation: Davis, K.E., Neinast, M.D., Sun, K., Skiles, W.M., Bills, J.D., Zehr, J.A., Zeve, D., Hahner, L.D., Cox, D.W., Gent, L.M., Xu, Y., Wang, Z.V., Khan, S.A., Clegg, D.J. 2013. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Molecular Metabolism 2:227-242.

Interpretive Summary: Obesity and type II diabetes are serious global health problems. Estrogens could provide beneficial effects on body weight and glucose balance. However, the mechanisms underlying these beneficial effects remain unknown. Metabolic characterization of these mouse models revealed that estrogens act in fat cells to prevent fat inflammation and improve glucose homeostasis. These findings highlighted estrogen actions in fat cells as the key regulator of body weight and glucose balance, and therefore we identified a potential target for development of novel therapies for obesity and/or diabetes.

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