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Effects of ERβ and ERα on OVX-induced changes in adiposity and insulin resistance
Journal article   Open access   Peer reviewed

Effects of ERβ and ERα on OVX-induced changes in adiposity and insulin resistance

Terese M Zidon, Jaume Padilla, Kevin L Fritsche, Rebecca J Welly, Leighton T McCabe, Olivia E Stricklin, Aaron Frank, Youngmin Park, Deborah J Clegg, Dennis B Lubahn, …
Journal of endocrinology, v 245(1)
Apr 2020
DOI: https://doi.org/10.1530/JOE-19-0321
PMID: 32053493
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://joe.bioscientifica.com/downloadpdf/journals/joe/245/1/JOE-19-0321.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1530/JOE-19-0321View
Published, Version of Record (VoR) Open

Abstract

Adiponectin - genetics Adiponectin - metabolism Adipose Tissue, White - metabolism Adiposity - genetics Animals Body Composition - genetics Energy Metabolism - genetics Estrogen Receptor alpha - deficiency Estrogen Receptor alpha - genetics Estrogen Receptor beta - deficiency Estrogen Receptor beta - genetics Female Gene Expression Humans Insulin Resistance - genetics Leptin - genetics Leptin - metabolism Mice, Inbred C57BL Mice, Knockout Ovariectomy Signal Transduction - genetics
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 (ERα) or estrogen receptor β (ERβ). We examined ovariectomized (OVX) and ovary-intactwild-type (WT), ERα-null (αKO), and ERβ-null (βKO) 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 αKO were ~25% fatter with reduced energy expenditure compared to age-matched INT WT controls and βKO mice (all P < 0.001). Following OVX, αKO mice did not increase adiposity or experience a further increase in IR, unlike WT and βKO, suggesting that loss of signaling through ERα mediates OVX-induced metabolic dysfunction. In fact, OVX in αKO mice (i.e., signaling through ERβ in the absence of ERα) resulted in reduced adiposity, adipocyte size, and IR (P < 0.05 for all). βKO mice responded adversely to OVX in terms of increased adiposity and development of IR. Together, these findings challenge the paradigm that ERα mediates metabolic protection over ERβ in all settings. These findings lead us to suggest that, following ovarian hormone loss, ERβ may mediate protective metabolic benefits.

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39 citations in Web of Science
33 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Endocrinology & Metabolism
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