Published Online
on March 15, 2004

A more recent version of this article appeared on March 30, 2004

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Submitted on July 30, 2003
Revised on November 19, 2003
Accepted on December 2, 2003

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

Michael Kuang BSc, Maria Febbraio PhD, Cory Wagg , Gary D. Lopaschuk PhD, and Jason R.B. Dyck PhD^*

From the Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada (M.K., C.W., G.D.L., J.R.B.D.), and Department of Medicine, Division of Hematology-Medical Oncology, Center of Vascular Biology, Weill Medical College of Cornell University, New York, NY (M.F.).

^* To whom correspondence should be addressed. E-mail: Jason.Dyck{at}ualberta.ca.

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.

Methods and 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 µU/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.

Key words: metabolism • fatty acids • ischemia

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