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Publication
Effects of ERß and ERa on OVX-induced changes in adiposity and insulin
resistance.
Authors Zidon TM, Padilla J, Fritsche KL, Welly RJ, McCabe LT, Stricklin OE, Frank A,
Park Y, Clegg DJ, Lubahn DB, Kanaley JA, Vieira-Potter VJ
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal The Journal of endocrinology
Year 2020
Date Published 4/1/2020
Volume : Pages 245 : 165 - 178
PubMed Reference 32053493
Abstract Loss of ovarian hormones leads to increased adiposity and insulin resistance
(IR), increasing the risk for cardiovascular and metabolic diseases. The purpose
of this study was to investigate whether the molecular mechanism behind the
adverse systemic and adipose tissue-specific metabolic effects of ovariectomy
requires loss of signaling through estrogen receptor alpha (ERa) or estrogen
receptor ß (ERß). We examined ovariectomized (OVX) and ovary-intactwild-type
(WT), ERa-null (aKO), and ERß-null (ßKO) female mice (age ~49 weeks; n =
7-12/group). All mice were fed a phytoestrogen-free diet (<15 mg/kg) and either
remained ovary-intact (INT) or were OVX and followed for 12 weeks. Body
composition, energy expenditure, glucose tolerance, and adipose tissue gene and
protein expression were analyzed. INT aKO were ~25% fatter with reduced energy
expenditure compared to age-matched INT WT controls and ßKO mice (all P <
0.001). Following OVX, aKO mice did not increase adiposity or experience a
further increase in IR, unlike WT and ßKO, suggesting that loss of signaling
through ERa mediates OVX-induced metabolic dysfunction. In fact, OVX in aKO mice
(i.e., signaling through ERß in the absence of ERa) resulted in reduced
adiposity, adipocyte size, and IR (P < 0.05 for all). ßKO mice responded
adversely to OVX in terms of increased adiposity and development of IR.
Together, these findings challenge the paradigm that ERa mediates metabolic
protection over ERß in all settings. These findings lead us to suggest that,
following ovarian hormone loss, ERß may mediate protective metabolic benefits.





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