Fatty acid translocase/CD36 deficiency does not energetically or functionally compromise hearts before or after ischemia.
BACKGROUND
Evidence from humans suggests that fatty acid translocase (FAT)/CD36 deficiency can lead to functionally and/or energetically compromised hearts, but the data are equivocal, and the subject remains controversial. In this report we assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in the intact heart and determined the effect of FAT/CD36 on energy metabolism during reperfusion of ischemic hearts.


RESULTS
Isolated working hearts from wild-type and FAT/CD36-knockout (KO) mice were perfused with Krebs-Henseleit solution containing 0.4 or 1.2 mmol/L [U-3H]palmitate, 5 mmol/L [U-14C]glucose, 2.5 mmol/L calcium, and 100 microU/mL insulin at a preload pressure of 11.5 mm Hg and afterload pressure of 50 mm Hg. Hearts were aerobically perfused for 30 minutes or aerobically perfused for 30 minutes, followed by 18 minutes of global no-flow ischemia and 40 minutes of aerobic reperfusion. Rates of fatty acid oxidation in FAT/CD36-KO hearts were significantly lower than in wild-type hearts at both concentrations of palmitate (0.4 or 1.2 mmol/L). In addition, hearts from FAT/CD36-KO mice displayed a compensatory increase in glucose oxidation rates. On aerobic reperfusion after ischemia, cardiac work of FAT/CD36-KO hearts recovered to the same extent as wild-type hearts.


CONCLUSIONS
FAT/CD36-deficient hearts are not energetically or functionally compromised and are not more sensitive to ischemic injury because glucose oxidation can compensate for the loss of fatty acid-derived ATP.
Kuang
Michael
M
Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Febbraio
Maria
M
Wagg
Cory
C
Lopaschuk
Gary D
GD
Dyck
Jason R B
JR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006439:Hemodynamics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010168:Palmitates / Q000378:metabolism
D018955:CD36 Antigens; D005227:Fatty Acids; D027361:Organic Anion Transporters; D010168:Palmitates; D000255:Adenosine Triphosphate; D005947:Glucose