Protein-mediated fatty acid uptake: regulation by contraction, AMP-activated protein kinase, and endocrine signals.
Fatty acid transport into heart and skeletal muscle occurs largely through a highly regulated protein-mediated mechanism involving a number of fatty acid transporters. Chronically altered muscle activity (chronic muscle stimulation, denervation) alters fatty acid transport by altering the expression of fatty acid transporters and (or) their subcellular location. Chronic exposure to leptin downregulates while insulin upregulates fatty acid transport by altering concomitantly the expression of fatty acid transporters. Fatty acid transport can also be regulated within minutes, by muscle contraction, AMP-activated protein kinase activation, leptin, and insulin, through induction of the translocation of fatty acid translocase (FAT)/CD36 from its intracellular depot to the plasma membrane. In insulin-resistant muscle, a permanent relocation of FAT/CD36 to the sarcolemma appears to account for the excess accretion of intracellular lipids that interfere with insulin signaling. Recent work has also shown that FAT/ CD36, but not plasma membrane associated fatty acid binding protein, is involved, along with carnitine palmitoyltransferase, in regulating mitochondrial fatty acid oxidation. Finally, studies in FAT/CD36 null mice indicate that this transporter has a key role in regulating fatty acid metabolism in muscle.
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
James G
JG
Nickerson
Iman
I
Momken
Carley R
CR
Benton
James
J
Lally
Graham P
GP
Holloway
Xiao-Xia
XX
Han
Jan F C
JF
Glatz
Adrian
A
Chabowski
Joost J F P
JJ
Luiken
Arend
A
Bonen
D055372:AMP-Activated Protein Kinases; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D005227:Fatty Acids; D006728:Hormones; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases