ESTROGEN RECEPTOR REGULATION OF GLUCOSE AND FAT METABOLISM IN THE SKELETAL MUSCLE AND ADIPOSE TISSUE

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

High Prevalence of Vitamin D Insufficiency in Farming and Nonfarming Populations in South Dakota: Associations With Parathyroid Hormone, Body Fat, and Bone Density

The purpose of this study was to investigate the role of lifestyle (farming vs nonfarming), age, season, and percent body fat on serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH). Serum 25-OHD concentrations were lower in winter than in summer and in older than in younger individuals. Dietary intake of vitamin D was associated with greater serum 25-OHD concentrations. A significant inverse relationship between PTH and 25-OHD was observed in older but not younger individuals. Trabecular volumetric bone mineral density was inversely associated with serum PTH, but not 25-OHD concentrations. Modern farm practices do not necessitate excessive sunlight exposure and that may help explain the lack of differences between farming and nonfarming populations

Altered estrogen receptor expression in skeletal muscle and adipose tissue of female rats fed a high-fat diet

Estrogen receptors (ERs) are expressed in adipose tissue and skeletal muscle, with potential implications for glucose metabolism and insulin signaling. Previous studies examining the role of ERs in glucose metabolism have primarily used knockout mouse models of ERα and ERβ, and it is unknown whether ER expression is altered in response to an obesity-inducing high-fat diet (HFD). The purpose of the current study was to determine whether modulation of glucose metabolism in response to a HFD in intact and ovariectomized (OVX) female rats is associated with alterations in ER expression. Our results demonstrate that a 6-wk HFD (60% calories from fat) in female rats induces whole body glucose intolerance with tissue-specific effects isolated to the adipose tissue, and no observed differences in insulin-stimulated glucose uptake, GLUT4, or ERα protein expression levels in skeletal muscle. In chow-fed rats, OVX resulted in decreased ERα with a trend toward decreased GLUT4 expression in adipose tissue. Sham-treated and OVX rats fed a HFD demonstrated a decrease in ERα and GLUT4 in adipose tissue. The HFD also increased activation of stress kinases (c-jun NH2-terminal kinase and inhibitor of κB kinase β) in the sham-treated rats and decreased expression of the protective heat shock protein 72 (HSP72) in both sham-treated and OVX rats. Our findings suggest that decreased glucose metabolism and increased inflammation in adipose tissue with a HFD in female rats could stem from a significant decrease in ERα expression