ABSTRACT:The effects of dehydroepiandrosterone (DHEA) on lipid metabolism and lipogenic gene mRNA expression in rats subjected to a high-fat diet were determined. Totally 75 rats were randomly divided into 5 groups: control group 1 fed a normal diet (NCG), and groups 2-5 fed a high-fat diet with 0 (HCG), 25 (HLG), 50 (HMG), 100 (HHG) mg DHEA per kg body weight via gavage once a day for 8 weeks, respectively. DHEA significantly decreased body weight in HMG group as compared with HCG group (P < 0.05). Hepatic triglyceride and total cholesterol contents were decreased in HMG and HHG groups (P < 0.05), and hepatic lipase activity in HMG group was higher (P < 0.01) than in HCG group. Fatty acid synthesis (FAS) mRNA level was decreased in HLG and HHG groups (P < 0.01), and sterol response element binding protein-1 (SREBP-1) mRNA level was decreased in HMG and HHG groups when compared with HCG group (P < 0.01). Acyl-CoA oxidase (ACO) and liver carnitine palmitoyl transferase-1 (LCPT-1) mRNA abundance was decreased in HLG and HHG groups (P < 0.01), whereas hormone sensitive lipase (HSL) mRNA level was increased in HMG group as compared with HCG group (P < 0.05). These results indicated that long-term administration of DHEA reduced the synthesis of endogenous triglycerides by inhibiting SREBP-1 and FAS expression, and augmented the lipolysis of exogenous triglycerides through enhancing HSL expression, which eventually led to reduced fat deposition in rats fed a high-fat diet.