Effect of short-term DHEA administration on liver metabolism of lean and obese rats

Lean and obese Zucker rats, 7-8 wk of age, were treated with dehydroepiandrosterone (DHEA) for either 3 or 7 days to determine the initial cellular event(s) that might be responsible for the antiobesity activity of DHEA. Epididymal, retroperitoneal, and brown adipose tissue weights were unaltered by either 3 or 7 days of DHEA treatment. Liver weight was not affected by 3 days of treatment but was 13 and 18% higher in 7-day DHEA-treated lean and obese rats, respectively, compared with their corresponding control group. Mitochondrial state 3 respiration rates with glutamate-malate and succinate as substrates were elevated by an average of 35% in 3- and 7-day DHEA-treated obese rats and by 15-20% in 7-day DHEA-treated lean rats compared with rates obtained in the corresponding control groups. State 3 respiration was not affected in 3-day DHEA-treated lean rats compared with control lean rats. The specific activities of long-chain fatty acyl-coenzyme A synthase and hydrolase and the levels of free CoA were increased by severalfold in cellular fractions of both DHEA-treated lean and obese rats compared with their respective control group. Hepatic malic enzyme activity, which was shown earlier to be elevated with long-term DHEA treatment, was unaltered by either 3 or 7 days of DHEA administration. The above results suggest the involvement of mitochondrial respiration and fatty acid deacylation/reacylation in the antiobesity mechanism of action of DHEA.