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Am J Physiol Endocrinol Metab (January 30, 2007). doi:10.1152/ajpendo.00579.2006
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Submitted on October 31, 2006
Accepted on January 12, 2007

A NULL MUTATION IN SKELETAL MUSCLE FAT/CD36 REVEALS ITS ESSENTIAL ROLE IN INSULIN-, AND AICAR-STIMULATED FATTY ACID METABOLISM

Arend Bonen1*, Xiao-Xia Han1, Daphna D.J. Habets2, Maria Febbraio3, Jan FC Glatz4, and Joost JFP Luiken5

1 Human Health and Nutritional Sciences, U of Guelph, Guelph, Canada
2 Department of Molecular Genetics, Maastricht University, Maastricht, Netherlands
3 Cell Biology, Lerner Research Institute, Cleveland, Ohio, United States
4 Department of Molecular Genetics, Maastricht University, NL- 6200 Maastricht, Netherlands
5 Deaprtment of Molecular Genetics, Maastricht University, Maastricht, Netherlands

* To whom correspondence should be addressed. E-mail: abonen{at}uoguelph.ca.

FAT/CD36 is involved in regulating the uptake of long chain fatty acids into muscle cells. However, the contribution of FAT/CD36 to fatty acid metabolism remains unknown. We examined the role of FAT/CD36 on fatty acid metabolism in perfused muscles (soleus, and red and white gastrocnemius of wild type (WT) and FAT/CD36 null (KO) mice. In general, in muscles of KO mice, a) insulin sensitivity and AICAR sensitivity were normal, b) key enzymes involved in fatty acid oxidation were altered minimally, or not at all, and c) except for an increase in soleus muscle FATP1and 4, these fatty acid transporters, were not altered in red and white gastrocnemius muscles, while FABPpm was not altered in any muscle. In KO muscles perfused under basal conditions (i.e. no insulin, no AICAR), rates of hindquarter fatty acid oxidation were reduced by 26%. Similarly, in oxidative, but not glycolytic muscles, the basal rates of triacylglycerol esterification were reduced by 40%. When muscles were perfused with insulin, the net increase in fatty acid esterification was 3-fold greater in the oxidative muscles of WT mice when compared to the oxidative muscles in KO mice. With AICAR-stimulation the net increase in fatty acid oxidation by hindquarter muscles was 3.7-fold greater in WT mice compared to KO mice. In conclusion, the present studies demonstrate that FAT/CD36 has a critical role in regulating fatty acid esterification and oxidation, particularly during stimulation with insulin or AICAR.




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