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-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.
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., K5.252, Dallas, TX 75390-8854, USA.
Kathryn E
KE
Davis
Michael
M
D Neinast
Kai
K
Sun
William
W
M Skiles
Jessica
J
D Bills
Jordan
J
A Zehr
Daniel
D
Zeve
Lisa
L
D Hahner
Derek
D
W Cox
Lana
L
M Gent
Yong
Y
Xu
Zhao
Z
V Wang
Sohaib
S
A Khan
Deborah J
DJ
Clegg
BAT, brown adipose tissue; ERα, estrogen receptor alpha; ERβ, estrogen receptor beta; Estrogen receptor alpha (ERα); Fibrosis; Inflammation; WAT, white adipose tissue; White adipose tissue (WAT)