Symposium 2: The fatty acid transporters of skeletal muscle

Regulation of fatty acid transport by fatty acid translocase/CD36

Arend Bonen^a1 c1, Shannon E. Campbell^a1a2, Carley R. Benton^a2, Adrian Chabowski^a1, Susan L. M. Coort^a3, Xiao-Xia Han^a1, Debby P. Y. Koonen^a3, Jan F. C. Glatz^a3 and Joost J. F. P. Luiken^a3

^a1 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada

^a2 Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada

^a3 Department of Molecular Genetics, CARIM, Maastricht University, 6200 MD, Maastricht, The Netherlands

Abstract

Fatty acid (FA) translocase (FAT)/CD36 is a key protein involved in regulating the uptake of FA across the plasma membrane in heart and skeletal muscle. A null mutation of FAT/CD36 reduces FA uptake rates and metabolism, while its overexpression increases FA uptake rates and metabolism. FA uptake into the myocyte may be regulated (a) by altering the expression of FAT/CD36, thereby increasing the plasmalemmal content of this protein (i.e. streptozotocin-induced diabetes, chronic muscle stimulation), or (b) by relocating this protein to the plasma membrane, without altering its expression (i.e. obese Zucker rats). By repressing FAT/CD36 expression, and thereby lowering the plasmalemmal FAT/CD36 (i.e. leptin-treated animals), the rate of FA transport is reduced. Within minutes of beginning muscle contraction or being exposed to insulin FA transport is increased. This increase is a result of the contraction- and insulin-induced translocation of FAT/CD36 from an intracellular depot to the cell surface. Neither PPARα nor PPARγ activation alter FAT/CD36 expression in muscle, despite the fact that PPARα activation increases FAT/CD36 by 80% in liver. A novel observation is that FAT/CD36 also appears to be involved in mitochondrial FA oxidation, as this protein is located on the mitochondrial membrane and seems to be required to participate in moving FA across the mitochondrial membrane. Clearly, FAT/CD36 has an important role in FA homeostasis in skeletal muscle and the heart.

Key Words:

• Cardiac;
• Myocytes;
• Skeletal muscle;
• Giant vesicles

Correspondence:

^c1 *Corresponding author: Dr Arend Bonen Fax: +1 519 763 59002, Email: abonen@uoguelph.ca