Plasmalemmal fatty acid transport is regulated in heart and skeletal muscle by contraction, insulin and leptin, and in obesity and diabetes.
It has been assumed that the uptake of long chain fatty acids (LCFAs) into skeletal muscle and the heart muscle, as well as other tissues, occurred via passive diffusion. In recent years our work has shown that the LCFA uptake into skeletal muscle is a highly regulated process. The use of giant sarcolemmal vesicles obtained from skeletal muscle and heart has been used to demonstrate that LCFA uptake into these tissues occurs via a protein-mediated mechanism involving the 40 kDa plasma membrane associated fatty acid binding protein (FABPpm) and the 88 kDa fatty acid translocase, the homologue of human CD36 (FAT/CD36). Both are ubiquitously expressed proteins and correlate with LCFA uptake into heart and muscle, consistent with the known differences in LCFA metabolism in these tissues. It has recently been found that FAT/CD36 is present in an intracellular (endosomal) compartment from which it can be translocated to the plasma membrane within minutes by muscle contraction and by insulin, to stimulate LCFA uptake. In rodent models of obesity and type 1 diabetes LCFA uptake into heart and muscle is also increased, either by permanently relocating FAT/CD36 to the plasma membrane without altering its expression (obesity) or by increasing the expression of both FAT/CD36 and FABPpm (type 1 diabetes). Chronic leptin treatment decreases LCFA transporters and transport in muscle. Clearly, recent evidence has established that LCFA uptake into heart and muscle is regulated acutely and chronically.
Bonen
A
A
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Benton
C R
CR
Campbell
S E
SE
Chabowski
A
A
Clarke
D C
DC
Han
X-X
XX
Glatz
J F C
JF
Luiken
J J F P
JJ
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology; D009765:Obesity / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats
D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D011506:Proteins