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ESTROGEN RECEPTOR REGULATION OF GLUCOSE AND FAT METABOLISM IN THE SKELETAL MUSCLE AND ADIPOSE TISSUE
Gorres, Brittany
Gorres, Brittany
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Abstract
Clinical studies suggest that postmenopausal women are at an increased risk for type 2 diabetes (T2D), and hormone replacement therapy can ameliorate this risk. Considerable clinical and experimental evidence exists demonstrating the ability of estrogen to modulate glucose metabolism in insulin responsive tissues such as the skeletal muscle and adipose tissue. Specifically, previous studies suggest estrogen receptor α (ERα) is involved in estrogen-mediated regulation of metabolism and is critical for the maintenance of whole body insulin action. However, very little is known regarding the mechanisms of action of ERα in insulin-responsive tissues. In addition, clinical evidence demonstrates that many women gain weight following menopause. This increase in body weight is accompanied by an increase in abdominal adipose tissue, which greatly increases one's risk for T2D. These studies are supported by animal models of ovariectomy (OVX) in which removal of the ovaries results in increased total body weight and fat pad weight, which are ameliorated by estrogen treatment. However, the mechanism of estrogen's action remains unknown. The purpose of our studies was to determine the effect of an obesity promoting high-fat diet (HFD) on skeletal muscle and adipose tissue estrogen receptor regulation and glucose metabolism in female rats with and without OVX. Furthermore we determined the effects of specific ERα activation on skeletal muscle glucose metabolism and adipose tissue triglyceride regulation. We found that a HFD decreased whole body glucose intolerance, without decreasing insulin-stimulated skeletal muscle glucose uptake, as previously found in male animal models. In female animal models, the HFD-induced decrease in whole body glucose tolerance likely occurred from alterations in the adipose tissue such as decreased glucose transporter 4 and ERα protein levels and increased activation of stress kinases. Furthermore, specific activation of ERα increased glucose uptake and potentiated the insulin signaling pathway in skeletal muscle. In addition, specific ERα activation decreased body weight and fat pad weight, decreased proteins involved in lipogenesis, and increased proteins involved in lipolysis. This information suggests novel roles of ERα in skeletal muscle glucose metabolism and adipocyte regulation and may help explain the metabolic differences between premenopausal and postmenopausal women.
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Date
2011-04-18
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University of Kansas
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Keywords
Physiology, Diabetes, Estradiol, Glut4, High-fat diet, Insulin, Ppt