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J Biol Chem, Vol. 274, Issue 38, 26761-26766, September 17, 1999
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From the Increasing evidence has implicated the membrane
protein CD36 (FAT) in binding and transport of long chain fatty acids
(FA). To determine the physiological role of CD36, we examined effects of its overexpression in muscle, a tissue that depends on FA for its
energy needs and is responsible for clearing a major fraction of
circulating FA. Mice with CD36 overexpression in muscle were generated
using the promoter of the muscle creatine kinase gene (MCK). Transgenic
(MCK-CD36) mice had a slightly lower body weight than control litter
mates. This reflected a leaner body mass with less overall adipose
tissue, as evidenced by magnetic resonance spectroscopy. Soleus muscles
from transgenic animals exhibited a greatly enhanced ability to oxidize
fatty acids in response to stimulation/contraction. This increased
oxidative ability was not associated with significant alterations in
histological appearance of muscle fibers. Transgenic mice had lower
blood levels of triglycerides and fatty acids and a reduced
triglyceride content of very low density lipoproteins. Blood
cholesterol levels were slightly lower, but no significant decrease in
the cholesterol content of major lipoprotein fractions was measured.
Blood glucose was significantly increased, while insulin levels were
similar in the fed state and higher in the fasted state. However,
glucose tolerance curves, determined at 20 weeks of age, were similar
in control and transgenic mice. In summary, the study documented,
in vivo, the role of CD36 to facilitate cellular FA uptake.
It also illustrated importance of the uptake process in muscle to
overall FA metabolism and glucose utilization.
Department of Physiology and Biophysics,
State University of New York, Stony Brook, New York 11794-8661, the
§ Department of Kinesiology, University of Waterloo,
Waterloo, Ontario N2L 3G1, Canada, the ¶ Department of Chemistry,
State University of New York, Stony Brook, New York 11794-3400, and the
Chemistry Department, Brookhaven National Laboratory,
Uptown, New York 11973
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