Skeletal muscle mitochondrial FAT/CD36 content and palmitate oxidation are not decreased in obese women

1 Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario; 2 Department of Medicine, McMaster University, Hamilton, Ontario, Canada; and 3 Thrombosis Research Laboratory, Otsuka Maryland Medicinal Laboratories, Rockville, Maryland Submitted 22 November 2006 ; accepted in final form 4 February 2007 A reduction in fatty acid oxidation has been associated with lipid accumulation and insulin resistance in the skeletal muscle of obese individuals. We examined whether this decrease in fatty acid oxidation was attributable to a reduction in muscle mitochondrial content and/or a dysfunction in fatty acid oxidation within mitochondria obtained from skeletal muscle of age-matched, lean [body mass index (BMI) = 23.3 ± 0.7 kg/m 2 ] and obese women (BMI = 37.6 ± 2.2 kg/m 2 ). The mitochondrial marker enzymes citrate synthase (–34%), -hydroxyacyl-CoA dehydrogenase (–17%), and cytochrome c oxidase (–32%) were reduced ( P < 0.05) in obese participants, indicating that mitochondrial content was diminished. Obesity did not alter the ability of isolated mitochondria to oxidize palmitate; however, fatty acid oxidation was reduced at the whole muscle level by 28% ( P < 0.05) in the obese. Mitochondrial fatty acid translocase (FAT/CD36) did not differ in lean and obese individuals, but mitochondrial FAT/CD36 was correlated with mitochondrial fatty acid oxidation ( r = 0.67, P < 0.05). We conclude that the reduction in fatty acid oxidation in obese individuals is attributable to a decrease in mitochondrial content, not to an intrinsic defect in the mitochondria obtained from skeletal muscle of obese individuals. In addition, it appears that mitochondrial FAT/CD36 may be involved in regulating fatty acid oxidation in human skeletal muscle. obesity; mitochondria; fatty acid translocase/CD36; transport proteins Address for reprint requests and other correspondence: G. Holloway, Dept. of Human Health & Nutritional Sciences, Univ. of Guelph, 50 Stone Rd., Guelph, Ontario, Canada N1G2W1 (e-mail: ghollowa{at}uoguelph.ca )