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Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice
Citation
Ribas, V and Nguyen, MTA and Henstridge, DC and Nguyen, A-K and Beaven, SW and Watt, MJ and Hevener, AL, Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice, American Journal of Physiology: Endocrinology and Metabolism, 298, (2) pp. E304-E319. ISSN 0193-1849 (2010) [Refereed Article]
Copyright Statement
Copyright 2010 the American Physiological Society
DOI: doi:10.1152/ajpendo.00504.2009
Abstract
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.
Item Details
Item Type: | Refereed Article |
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Keywords: | estrogen receptor-α, estrogen action, fatty acid metabolism, insulin action |
Research Division: | Biological Sciences |
Research Group: | Biochemistry and cell biology |
Research Field: | Cell metabolism |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Henstridge, DC (Dr Darren Henstridge) |
ID Code: | 133327 |
Year Published: | 2010 |
Web of Science® Times Cited: | 211 |
Deposited By: | Health Sciences |
Deposited On: | 2019-06-24 |
Last Modified: | 2019-07-31 |
Downloads: | 0 |
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