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.
Mohan
P F
PF
Hormel Institute, University of Minnesota, Austin 55912.
Cleary
M P
MP
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003065:Coenzyme A / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004435:Eating; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism*; D009929:Organ Size; D010101:Oxygen Consumption; D051381:Rats; D011924:Rats, Zucker; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003687:Dehydroepiandrosterone; D008291:Malate Dehydrogenase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D003065:Coenzyme A