Contribution of FAT/CD36 to the regulation of skeletal muscle fatty acid oxidation: an overview.
Long chain fatty acids (LCFAs) are an important substrate for ATP production within the skeletal muscle. The process of LCFA delivery from adipose tissue to muscle mitochondria involves many regulatory steps. Recently, it has been recognized that LCFA oxidation is not only dependent on LCFA delivery to the muscle, but also on regulatory steps within the muscle. Increasing selected fatty acid binding proteins/transporters on the plasma membrane facilitates a very rapid LCFA increase into the muscle, independent of any changes in LCFA delivery to the muscle. Such a mechanism of LCFA transporter translocation is activated by muscle contraction. Intramuscular triacylglycerols may also be hydrolysed to provide fatty acids for mitochondrial oxidation, particularly during exercise, when hormone-sensitive lipase and other enzymes are activated. Mitochondrial LCFA entry is also highly regulated. This however does not involve only the malonyl CoA carnitine palmitoyltransferase-I (CPTI) axis. Exercise-induced fatty acid entry into mitochondria is also regulated by at least one of the proteins (FAT/CD36) that also regulates plasma membrane fatty acid transport. Among individuals, differences in mitochondrial fatty acid oxidation appear to be correlated with the content of mitochondrial CPTI and FAT/CD36. This paper provides a brief overview of mechanisms that regulate LCFA uptake and oxidation in skeletal muscle during exercise and in obesity. We focus largely on our own work on FAT/CD36, which contributes to regulating, in a coordinated fashion, LCFA uptake across the plasma membrane and the mitochondrial membrane. Very little is known about the roles of FATP1-6 on fatty acid transport in skeletal muscle.
Department of Human Health and Nutritional Sciences University of Guelph, Guelph, ON, Canada.
G P
GP
Holloway
J J F P
JJ
Luiken
J F C
JF
Glatz
L L
LL
Spriet
A
A
Bonen
D000217:Acyltransferases / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D018955:CD36 Antigens / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction
D018955:CD36 Antigens; D005227:Fatty Acids; D007328:Insulin; D008565:Membrane Proteins; D000217:Acyltransferases