title: Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle.
abstract: Chronic leptin administration reduces triacylglycerol content in skeletal muscle. We hypothesized that chronic leptin treatment, within physiologic limits, would reduce the fatty acid uptake capacity of red and white skeletal muscle due to a reduction in transport protein expression (fatty acid translocase (FAT/CD36) and plasma membrane-associated fatty acid-binding protein (FABPpm)) at the plasma membrane. Female Sprague-Dawley rats were infused for 2 weeks with leptin (0.5 mg/kg/day) using subcutaneously implanted miniosmotic pumps. Control and pair-fed animals received saline-filled implants. Leptin levels were significantly elevated (approximately 4-fold; p < 0.001) in treated animals, whereas pair-fed treated animals had reduced serum leptin levels (approximately -2-fold; p < 0.01) relative to controls. Palmitate transport rates into giant sarcolemmal vesicles were reduced following leptin treatment in both red (-45%) and white (-84%) skeletal muscle compared with control and pair-fed animals (p < 0.05). Leptin treatment reduced FAT mRNA (red, -70%, p < 0.001; white, -48%, p < 0.01) and FAT/CD36 protein expression (red, -32%; p < 0.05) in whole muscle homogenates, whereas FABPpm mRNA and protein expression were unaltered. However, in leptin-treated animals plasma membrane fractions of both FAT/CD36 and FABPpm protein expression were significantly reduced in red (-28 and -34%, respectively) and white (-44 and -56%, respectively) muscles (p < 0.05). Across all experimental treatments and muscles, palmitate uptake by giant sarcolemmal vesicles was highly correlated with the plasma membrane FAT/CD36 protein (r = 0.88, p < 0.01) and plasma membrane FABPpm protein (r = 0.94, p < 0.01). These studies provide the first evidence that protein-mediated long chain fatty acid transport is subject to long term regulation by leptin.
authors.affiliation: Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario N1G 2W1, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Steinberg
authors.forename: David J
authors.initials: DJ
authors.lastname: Dyck
authors.forename: Jorges
authors.initials: J
authors.lastname: Calles-Escandon
authors.forename: Narendra N
authors.initials: NN
authors.lastname: Tandon
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018955:CD36 Antigens; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D004435:Eating; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger