New insights into long-chain fatty acid uptake by heart muscle: a crucial role for fatty acid translocase/CD36.
Long-chain fatty acids are an important source of energy for several cell types, in particular for the heart muscle cell. Three different proteins, fatty acid translocase (FAT)/CD36, fatty acid transport protein and plasma membrane fatty acid binding protein, have been identified as possible membrane fatty acid transporters. Much information has been accumulated recently about the fatty acid transporting function of FAT/CD36. Several experimental models to study the influence of altered FAT/CD36 expression on fatty acid homoeostasis have been identified or developed, and underscore the importance of FAT/CD36 for adequate fatty acid transport. These models include the FAT/CD36 null mouse, the spontaneously hypertensive rat and FAT/CD36-deficient humans. The fatty acid transporting role of FAT/CD36 is further demonstrated in mice overexpressing muscle-specific FAT/CD36, and in transgenic mice generated using a genetic-rescue approach. In addition, a wealth of information has been gathered about the mechanisms that regulate FAT/CD36 gene expression and the presence of functional FAT/CD36 on the plasma membrane. Available data also indicate that FAT/CD36 may have an important role in the aetiology of cardiac disease, especially cardiac hypertrophy and diabetic cardiomyopathy. This review discusses our current knowledge of the three candidate fatty acid transporters, the metabolic consequences of alterations in FAT/CD36 levels in different models, and the mechanisms that have been identified for FAT/CD36 regulation.
Brinkmann
Joep F F
JF
Cardiovascular Research Institute Maastricht (CARIM), Department of Physiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Abumrad
Nada A
NA
Ibrahimi
Azeddine
A
van der Vusse
Ger J
GJ
Glatz
Jan F C
JF
D000818:Animals; D018955:CD36 Antigens; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism*
D018955:CD36 Antigens; D005227:Fatty Acids; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters