There is substantial molecular, biochemical and physiologic evidence that long-chain
fatty acid transport involves a
protein-mediated process. A number of
fatty acid transport proteins have been identified, and for unknown reasons, some of these are coexpressed in the same tissues. In muscle and heart FAT/CD36 and FABPpm appear to be key transporters. Both
proteins are regulated acutely (within minutes) and chronically (hours to days) by selected physiologic stimuli (
insulin,
AMP kinase activation). Acute regulation involves the translocation of FAT/CD36 by
insulin, muscle contraction and
AMP kinase activation, while FABPpm is induced to translocate by muscle contraction and
AMP kinase activation, but not by
insulin.
Protein expression ofFAT/CD36 and FABPpm is regulated by prolonged
AMP kinase activation (heart) or increased muscle contraction. Prolonged
insulin exposure increases the expression of FAT/CD36 but not FABPpm. Trafficking of
fatty acid transporters between an intracellular compartment(s) and the plasma membrane is altered in
insulin-resistant skeletal muscle, as some FAT/CD36 is permanently relocated to plasma membrane, thereby contributing to
insulin resistance due to the increased influx of
fatty acids into muscle cells. Studies in FAT/CD36 null mice have revealed that this transporter is key to regulating the increase in the rate of
fatty acid metabolism in heart and skeletal muscle. It appears based on a number of experiments that FAT/CD36 and FABPpm may collaborate to increase the rates of
fatty acid transport, as these
proteins co-immunoprecipitate.