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Originally published In Press as doi:10.1074/jbc.M107683200 on November 29, 2001

J. Biol. Chem., Vol. 277, Issue 11, 8854-8860, March 15, 2002
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Chronic Leptin Administration Decreases Fatty Acid Uptake and Fatty Acid Transporters in Rat Skeletal Muscle*

Gregory R. SteinbergDagger §, David J. DyckDagger , Jorges Calles-Escandon, Narendra N. Tandon||, Joost J. F. P. Luiken**Dagger Dagger , Jan F. C. Glatz§§, and Arend Bonen¶¶

From the Dagger  Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario N1G 2W1, Canada,  Glaxo SmithKline, Miami, Florida 33134, the || Thrombosis Research Laboratory, Otsuka Maryland Research Institute, Rockville, Maryland 20850, the ** Department of Physiology, Maastricht University, 6200 MD Maastricht, The Netherlands, and the §§ Department of Kinesiology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada

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 (~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.


* This work was supported by grants from the Canadian Institutes of Health Research (to A. B.) and the Natural Sciences and Engineering Research Council of Canada (to D. J. D. and A. B.) and by Netherlands Heart Foundation Grant D98.012 (to J. F. C. G. and J. J. F. P. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of a Natural Sciences and Engineering Research Council postgraduate scholarship.

Dagger Dagger A Dekker postdoctoral fellow of the Netherlands Heart Foundation.

¶¶ To whom correspondence should be addressed: Dept. of Kinesiology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Tel.: 519-888-1211 (ext. 5214); Fax: 519-746-6776; E-mail: abonen@healthy.uwaterloo.ca.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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