Regulation of fatty acid transport by fatty acid translocase/CD36.
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 PPAR alpha nor PPAR gamma activation alter FAT/CD36 expression in muscle, despite the fact that PPAR alpha 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.
Bonen
Arend
A
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada. abonen@uoguelph.ca
Campbell
Shannon E
SE
Benton
Carley R
CR
Chabowski
Adrian
A
Coort
Susan L M
SL
Han
Xiao-Xia
XX
Koonen
Debby P Y
DP
Glatz
Jan F C
JF
Luiken
Joost J F P
JJ
D001693:Biological Transport, Active / Q000502:physiology*; D018955:CD36 Antigens / Q000502:physiology*; D002462:Cell Membrane; D015444:Exercise / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D015398:Signal Transduction
D018955:CD36 Antigens; D005227:Fatty Acids