Metabolic alterations after dehydroepiandrosterone treatment in Zucker rats

Dehydroepiandrosterone (DHEA) is a known noncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD). In the present investigation, the effects of chronic DHEA treatment on G6PD and several other enzymes involved in lipid metabolism were examined in lean and obese Zucker rats. Significant decreases in body weight were found in DHEA-treated rats in comparison with nontreated rats. In lean rats, DHEA treatment did not decrease either liver or adipose tissue G6PD and fatty acid synthetase activity, but malic enzyme activity was increased. In obese rats, decreased liver and adipose tissue G6PD and fatty acid synthetase activities were found. Malic enzyme activity in liver of obese DHEA rats was increased but not in adipose tissue. Adipose tissue lipoprotein lipase activity was decreased in both lean and obese DHEA rats. Serum insulin in obese DHEA rats was also decreased compared with control obese rats. These results indicate that the inhibition of G6PD may not be the mechanism of action of the antiobesity effect of DHEA. However, the metabolic effects of DHEA seen in obese rats may contribute to its antiobesity action.