Defect in human myocardial long-chain fatty acid uptake is caused by FAT/CD36 mutations.
Because of the importance of long-chain fatty acids (LCFAs) as a myocardial energy substrate, myocardial LCFA metabolism has been of particular interest for the understanding of cardiac pathophysiology. Recently, by using radiolabeled LCFA analogues, myocardial LCFA metabolism has been clinically evaluated, which revealed a total defect of myocardial LCFA accumulation in a small number of subjects. The mechanism for the cellular LCFA uptake process is still disputable, but recent results suggest that fatty acid translocase (FAT)/CD36 is a transporter in the heart. In the present study, we analyzed mutations and protein expression of the FAT/CD36 gene in 47 patients who showed total lack of the accumulation of a radiolabeled LCFA analogue in the heart. All the patients carried two mutations in the FAT/CD36 gene, and expression of the FAT/CD36 protein was not detected on either platelet or monocyte membranes. Our results showed the link between mutations of the FAT/CD36 gene and a defect in the accumulation of LCFAs in the human heart.
Tanaka
T
T
Third Division, Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. in3024@poh.osaka-med.ac.jp
Nakata
T
T
Oka
T
T
Ogawa
T
T
Okamoto
F
F
Kusaka
Y
Y
Sohmiya
K
K
Shimamoto
K
K
Itakura
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D007462:Iodobenzenes / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D027361:Organic Anion Transporters; D012189:Retrospective Studies; D015899:Tomography, Emission-Computed, Single-Photon
D018955:CD36 Antigens; D005227:Fatty Acids; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; C049338:iodofiltic acid