Leptin and insulin modulate nutrient partitioning and weight loss in ob/ob mice through regulation of long-chain fatty acid uptake by adipocytes.
Leptin treatment of ob/ob mice leads to weight loss appreciably greater than that in pair-fed mice. To test whether this "extra" weight loss is mediated by leptin-induced alterations in nutrient partitioning, the effects in ob/ob mice of subcutaneous leptin infusion (500 ng/h for <or=21 d) on adipocyte fatty acid uptake and transporter gene expression were examined. Mice were initially hyperinsulinemic (5.25 +/- 1.57 nmol/L). Plasma insulin decreased by 55 +/- 10% within 8 h of leptin infusion, declining progressively to normal by d 14. The V(max) for saturable adipocyte fatty acid uptake fell from 31.1 +/- 5.6 to 25.2 +/- 4.0 pmol/(s. 50000 cells) (P < 0.05) by 24 h, and to a normal rate (8.0 +/- 0.8 pmol/(s. 50000 cells) by d 21 (P > 0.5 vs. normal C57BL/6J controls). Adipocyte mRNA levels for plasma membrane fatty acid binding protein and fatty acid translocase, putative fatty acid transporters that are up-regulated three- to fourfold in adipocytes from ob/ob mice, had also normalized by d 21. The initial changes in V(max) preceded decreases in food intake and body weight by at least 24 h. In pair-fed mice, insulin levels, V(max) and body weight all declined more slowly than in leptin-treated mice, and all remained significantly elevated compared with normal values at d 21. The data suggest that insulin up-regulates and leptin down-regulates adipocyte fatty acid uptake, leading to alterations in fatty acid partitioning that affect adiposity.
Fan
Xinqing
X
Departments of Medicine, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Bradbury
Michael W
MW
Berk
Paul D
PD
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D018955:CD36 Antigens; D048429:Cell Size; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D020738:Leptin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D027361:Organic Anion Transporters / Q000235:genetics; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin; D015431:Weight Loss / Q000502:physiology*
D018955:CD36 Antigens; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D001219:Aspartate Aminotransferases