Abstract
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.
Highlights
Our previous work with rat adipocytes presented evidence that membrane transport of long chain fatty acids (FA)1 had a protein-facilitated component [1, 2]
We report that muscle-targeted overexpression of CD36 was associated with enhanced muscle FA oxidation and with alterations in body fat and in blood levels of FA, triglycerides, cholesterol, glucose, and insulin
This study examined the metabolic effects of overexpressing CD36 in muscle tissues
Summary
Vol 274, No 38, Issue of September 17, pp. 26761–26766, 1999 Printed in U.S.A. Muscle-specific Overexpression of FAT/CD36 Enhances Fatty Acid Oxidation by Contracting Muscle, Reduces Plasma Triglycerides and Fatty Acids, and Increases Plasma Glucose and Insulin*. 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. To directly assess the role of CD36 in mediating muscle FA uptake, in vivo, we generated a transgenic mouse model with overexpression of CD36 targeted to muscle tissues. We hypothesized that if CD36 determined FA uptake and utilization by muscle, its overexpression in this tissue should play a uniquely important role in regulating metabolism in general. We report that muscle-targeted overexpression of CD36 was associated with enhanced muscle FA oxidation and with alterations in body fat and in blood levels of FA, triglycerides, cholesterol, glucose, and insulin
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