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Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice

journal contribution
posted on 2023-05-20, 04:41 authored by Ribas, V, Nguyen, MTA, Darren HenstridgeDarren Henstridge, Nguyen, A-K, Beaven, SW, Watt, MJ, Hevener, AL
Impaired estrogen action is associated with the metabolic syndrome in humans. We sought to determine whether impaired estrogen action in female C57Bl6 mice, produced by whole body Esr1 ablation, could recapitulate aspects of this syndrome, including inflammation, insulin resistance, and obesity. Indeed, we found that global knockout (KO) of the estrogen receptor (ER)α leads to reduced oxygen uptake and caloric expenditure compared with wild-type (WT) mice. In addition, fasting insulin, leptin, and PAI-1 levels were markedly elevated, whereas adiponectin levels were reduced in normal chow-fed KO. Furthermore, ERα-KO mice exhibited impaired glucose tolerance and marked skeletal muscle insulin resistance that was accompanied by the accumulation of bioactive lipid intermediates, inflammation, and diminished PPARα, PPARδ, and UCP2 transcript levels. Although the relative glucose intolerance and insulin resistance phenotype in KO mice became more severe with high-fat feeding, WT mice were refractory to these dietary-induced effects, and this protection coincided with a marked increase in circulating adiponectin and heat shock protein 72 levels in muscle, liver, and fat. These data indicate that ERα is critical for the maintenance of whole body insulin action and protection against tissue inflammation during both normal chow and high-fat feeding.

History

Publication title

American Journal of Physiology: Endocrinology and Metabolism

Volume

298

Pagination

E304-E319

ISSN

0193-1849

Department/School

School of Health Sciences

Publisher

Amer Physiological Soc

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814

Rights statement

Copyright 2010 the American Physiological Society

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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