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BACKGROUND: Fatty acid and glucose transporters translocate between the sarcolemma and intracellular compartments to regulate substrate metabolism acutely. We hypothesised that during ischemia fatty acid translocase (FAT/CD36) would translocate away from the sarcolemma to limit fatty acid uptake when fatty acid oxidation is inhibited. METHODS AND RESULTS: Wistar rat hearts were perfused during preischemia, low-flow ischemia, and reperfusion, using (3)H-substrates for measurement of metabolic rates, followed by metabolomic analysis and subcellular fractionation. During ischemia, there was a 32% decrease in sarcolemmal FAT/CD36 accompanied by a 95% decrease in fatty acid oxidation rates, with no change in intramyocardial lipids. Concomitantly, the sarcolemmal content of the glucose transporter, GLUT4, increased by 90% during ischemia, associated with an 86% increase in glycolytic rates, 45% decrease in glycogen content, and a 3-fold increase in phosphorylated AMP-activated protein kinase. Following reperfusion, decreased sarcolemmal FAT/CD36 persisted, but fatty acid oxidation rates returned to preischemic levels, resulting in a 35% decrease in myocardial triglyceride content. Elevated sarcolemmal GLUT4 persisted during reperfusion; in contrast, glycolytic rates decreased to 30% of preischemic rates, accompanied by a 5-fold increase in intracellular citrate levels and restoration of glycogen content. CONCLUSIONS: During ischemia, FAT/CD36 moved away from the sarcolemma as GLUT4 moved toward the sarcolemma, associated with a shift from fatty acid oxidation to glycolysis, while intramyocardial lipid accumulation was prevented. This relocation was maintained during reperfusion, which was associated with replenishing glycogen stores as a priority, occurring at the expense of glycolysis and mediated by an increase in citrate levels.

Original publication

DOI

10.1161/CIRCHEARTFAILURE.112.000342

Type

Journal article

Journal

Circ Heart Fail

Publication Date

01/09/2013

Volume

6

Pages

1058 - 1066

Keywords

acute metabolic changes, fatty acid metabolism, glucose metabolism, ischemia reperfusion, Animals, Antigens, CD36, Disease Models, Animal, Energy Metabolism, Fatty Acids, Glucose Transporter Type 4, Glycogen, Glycolysis, Male, Metabolomics, Myocardial Ischemia, Myocardial Reperfusion, Myocardium, Oxidation-Reduction, Protein Transport, Rats, Rats, Wistar, Sarcolemma, Subcellular Fractions