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Am J Physiol Endocrinol Metab 292: E1740-E1749, 2007. First published January 30, 2007; doi:10.1152/ajpendo.00579.2006
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A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin- and AICAR-stimulated fatty acid metabolism

Arend Bonen,1 Xiao-Xia Han,1 Daphna D. J. Habets,2 Maria Febbraio,3 Jan F. C. Glatz,2 and Joost J. F. P. Luiken2,4

1Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; 2Department of Molecular Genetics, Maastricht University, Maastricht, The Netherlands; 3Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Cleveland, Ohio; and 4Department of Biochemical Physiology and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands

Submitted 31 October 2006 ; accepted in final form 12 January 2007

Fatty acid translocase (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, 1) insulin sensitivity and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) sensitivity were normal, 2) key enzymes involved in fatty acid oxidation were altered minimally or not at all, and 3) except for an increase in soleus muscle FATP1 and FATP4, these fatty acid transporters were not altered in red and white gastrocnemius muscles, whereas plasma membrane-bound fatty acid binding protein 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 threefold greater in the oxidative muscles of WT mice compared with 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 compared with 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.

perfusion; palmitate; esterification; oxidation; fatty transport proteins 1 and 2; plasma membrane-bound fatty acid binding protein; 5-amino-imidazole-4-carboxamide-1-beta-D-ribofuranoside



Address for reprint requests and other correspondence: A. Bonen, Dept. of Human Health and Nutritional Science, Univ. of Guelph, Guelph, Ontario, Canada N1G 2W1 (e-mail: abonen{at}uoguelph.ca)




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