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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
Chronic Leptin Administration Decreases Fatty Acid Uptake and
Fatty Acid Transporters in Rat Skeletal Muscle*
Gregory R.
Steinberg §,
David J.
Dyck ,
Jorges
Calles-Escandon¶,
Narendra N.
Tandon ,
Joost J. F. P.
Luiken** ,
Jan F. C.
Glatz§§, and
Arend
Bonen¶¶
From the 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.

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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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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