Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes.
The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng.mL-1) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supra-physiological insulin concentration (10 000 microU.mL-1). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng. mL-1, respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system.
Ceddia
R B
RB
Department of Physical Education, Fluminense Federal University, Niterói, Rio de Janeiro, Brasil.
William
W N
WN
Lima
F B
FB
Flandin
P
P
Curi
R
R
Giacobino
J P
JP
D000085:Acetates / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007473:Ion Channels; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D008055:Lipids / Q000096:biosynthesis*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D019301:Oleic Acid / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D000085:Acetates; D002352:Carrier Proteins; D005227:Fatty Acids; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008055:Lipids; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; C000604393:Ucp3 protein, mouse; C000604394:Ucp3 protein, rat; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D019301:Oleic Acid; D008291:Malate Dehydrogenase; C031917:malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+); D002950:Citrate (si)-Synthase