Differential Translocation of the Fatty Acid Transporter, FAT/CD36, and the Glucose Transporter, GLUT4, Coordinates Changes in Cardiac Substrate Metabolism During Ischemia and Reperfusion

作者：Heather Lisa C^*; Pates Katharine M; Atherton Helen J; Cole Mark A; Ball Daniel R; Evans Rhys D; Glatz Jan F; Luiken Joost J; Griffin Julian L; Clarke Kieran

来源：Circulation-Heart Failure, 2013, 6(5): 1058-1066.

DOI：10.1161/CIRCHEARTFAILURE.112.000342

• acute metabolic changes
• fatty acid metabolism
• glucose metabolism
• ischemia reperfusion

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. %26lt;br%26gt;Methods and Results Wistar rat hearts were perfused during preischemia, low-flow ischemia, and reperfusion, using H-3-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. %26lt;br%26gt;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.

• 出版日期2013-9