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

in Journal of Endocrinology
Authors:
Terese M Zidon Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Jaume Padilla Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA

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Kevin L Fritsche Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Rebecca J Welly Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Leighton T McCabe Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Olivia E Stricklin Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Aaron Frank Department of Biomedical Sciences, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

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Youngmin Park Department of Exercise and Health Science, Incheon National University, Incheon, South Korea

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Deborah J Clegg College of Nursing and Health Professions, Drexel University, Philadelphia, Pennsylvania, USA

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Dennis B Lubahn Department of Biochemistry, University of Missouri, Columbia, Missouri, USA

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Jill A Kanaley Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Victoria J Vieira-Potter Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA

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Correspondence should be addressed to V J Vieira-Potter: vieirapotterv@missouri.edu
DOI:
https://doi.org/10.1530/JOE-19-0321
Volume/Issue:
Volume 245: Issue 1
Article Type:
Research Article
Page Range:
165–178
Online Publication Date:
Apr 2020
Copyright:
© 2020 Society for Endocrinology 2020
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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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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
14
Article Type:
Research Article
Received Date:
09 Feb 2020
Accepted Date:
13 Feb 2020
Print Publication Date:
01 Apr 2020
Online Publication Date:
Apr 2020
Keywords:
menopause; metabolism; glucose metabolism; estrogen receptors; adipose tissue

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