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(Circulation. 2004;109:1550-1557.)
© 2004 American Heart Association, Inc.

Basic Science Reports

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; 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.).

Reprint requests to Dr Jason R.B. Dyck, 474 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. E-mail Jason.Dyck{at}ualberta.ca

Received July 30, 2003; de novo received September 25, 2003; revision received November 19, 2003; accepted December 2, 2003.

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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