Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone.
Dehydroepiandrosterone (DHEA) treatment of rats decreases gain of body weight without affecting food intake; simultaneously, the activities of liver malic enzyme and cytosolic glycerol-3-P dehydrogenase are increased. In the present study experiments were conducted to test the possibility that DHEA enhances thermogenesis and decreases metabolic efficiency via transhydrogenation of cytosolic NADPH into mitochondrial FADH2 with a consequent loss of energy as heat. The following results provide evidence which supports the proposed hypothesis: (a) the activities of cytosolic enzymes involved in NADPH production (malic enzyme, cytosolic isocitrate dehydrogenase, and aconitase) are increased after DHEA treatment; (b) cytosolic glycerol-3-P dehydrogenase may use both NAD+ and NADP+ as coenzymes; (c) activities of both cytosolic and mitochondrial forms of glycerol-3-P dehydrogenase are increased by DHEA treatment; (d) cytosol obtained from DHEA-treated rats synthesizes more glycerol-3-P during incubation with fructose-1,6-P2 (used as source of dihydroxyacetone phosphate) and NADP+; the addition of citrate in vitro further increases this difference; (e) mitochondria prepared from DHEA-treated rats more rapidly consume glycerol-3-P added exogenously or formed endogenously in the cytosol in the presence of fructose-1,6-P2 and NADP+.
Bobyleva
V
V
Institute of General Pathology, University of Modena, Italy.
Kneer
N
N
Bellei
M
M
Battelli
D
D
Lardy
H A
HA
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D003600:Cytosol / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004099:Dihydroxyacetone Phosphate / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005182:Flavin-Adenine Dinucleotide / Q000031:analogs & derivatives / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism; D006019:Glycolysis; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism
D002951:Citrates; D005994:Glycerophosphates; D005182:Flavin-Adenine Dinucleotide; C058805:1,5-dihydro-FAD; D019343:Citric Acid; D003687:Dehydroepiandrosterone; D009249:NADP; D004099:Dihydroxyacetone Phosphate; C029620:alpha-glycerophosphoric acid; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase