DHEA PROTECTS AGAINST VISCERAL OBESITY AND MUSCLE INSULIN-RESISTANCE IN RATS FED A HIGH-FAT DIET

Visceral obesity is frequently associated with muscle insulin resistan ce. Rats fed a high-fat diet rapidly develop obesity and insulin resis tance. Dehydroepiandrosterone (DHEA) has been reported to protect agai nst the development of obesity. This study tested the hypothesis that DHEA protects against the increase in visceral fat and the development of muscle insulin resistance induced by a high-fat diet in rats. Feed ing rats a diet providing 50% of the energy as fat for 4 wk resulted i n a twofold greater visceral fat mass and a 50% lower rate of maximall y insulin-stimulated muscle 2-deoxyglucose (2-DG) uptake compared with controls. Rats fed the high-fat diet plus 0.3% DHEA were largely prot ected against the increase in visceral fat (+11.3 g in high fat vs. +2 .9 g in high fat plus DHEA, compared with controls) and against the de crease in insulin-stimulated muscle 2-DG uptake (0.94 +/- 0.15 mu mol. ml(-1).20 min(-1), controls; 0.46 +/- 0.06 mu mol.ml(-1).20 min(-1), h igh-fat diet; 0.78 +/- 0.07 mu mol.ml(-1).20 min(-1), high fat + DHEA) . DHEA did not affect food intake. These results show that DHEA has a protective effect against accumulation of visceral fat and development of muscle insulin resistance in rats fed a high-fat diet.