DHEA TREATMENT REDUCES FAT ACCUMULATION AND PROTECTS AGAINST INSULIN-RESISTANCE IN MALE RATS

The purpose of this study,uas to determine whether administration of d ehydroepiandrosterone (DHEA) protects male rats against the accumulati on of body fat and development of insulin resistance with advancing ag e. We found that supplementation of the diet with 0.3% DHEA between th e ages of 5 months and approximate to 25 months resulted iii a signifi cantly lower final body weight (DHEA, 593 +/- 18 g vs control, 668 +/- 12 g, p < 0.02), despite no decrease ill food intake. Lean body mass was unaffected by the DHEA, and the lower body weight was due to a app roximate to 25% reduction in body fat. The rate of glucose disposal du ring a euglycemic, hyperinsulinemic clamp was 30% higher in the DHEA g roup than in the sedentary controls due to a greater insulin responsiv eness, The DHEA administration was as effective in reducing body fat c ontent and maintaining insulin responsiveness as exercise in the form of voluntary wheel running. The DHEA had no significant effect on musc le GLUT4 content. A preliminary experiment provided evidence suggestin g that muscle insulin signaling, as reflected Ct binding of phosphatid ylinositol 3-kinase to the insulin receptor substrate-1, was enhanced in the DHEA-treated and wheel running groups as compared to controls. These results provide evidence that DHEA, like exercise, protects agai nst excess fat accumulation and development of insulin resistance in r ats.