Visceral obesity is frequently associated with muscle insulin resistance. Rats 
fed a high-fat diet rapidly develop obesity and insulin resistance. 
Dehydroepiandrosterone (DHEA) has been reported to protect against 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. Feeding rats a diet providing 50% 
of the energy as fat for 4 wk resulted in a twofold greater visceral fat mass 
and a 50% lower rate of maximally insulin-stimulated muscle 2-deoxyglucose 
(2-DG) uptake compared with controls. Rats fed the high-fat diet plus 0.3% DHEA 
were largely protected 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 
decrease in insulin-stimulated muscle 2-DG uptake (0.94 +/- 0.15 mumol.ml-1.20 
min-1, controls; 0.46 +/- 0.06 mumol.ml-1.20 min-1, high-fat diet; 0.78 +/- 0.07 
mumol.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.