Methyl palmitate protects heart against ischemia/reperfusion-induced injury through G-protein coupled receptor 40-mediated activation of the PI3K/AKT pathway

This study aimed to investigate whether methyl palmitate (MP) exerts cardioprotective effect against the ischemia/reperfusion (I/R) injury and its mechanisms underlying. The cultured adult cardiomyocytes were treated with vehicle or lactic acid ischemic buffer (pH 6.8) during hypoxia/reoxygenation. In addition, the cardioprotective effect of MP was evaluated using the ex vivo heart model of I/R injury. Here, we found that MP significantly reduced the I/R-induced cardiomyocyte death. Treatment with GW1100 (a GPR40-antagonist) or wortmannin (a phosphatidylinositol 3-kinase, PI3K, specific inhibitor) significantly attenuated the level of phospho-AKT (p-AKT) and abolished the MP-induced cardioprotection against the I/R-induced injury. Using the ex vivo I/R model, we also demonstrated that pretreatment with MP significantly reduced the size of myocardial infarction and the levels of cleaved-caspase 3 and MDA, and increased the protein levels of GPR40 and p-AKT induced by I/R. The cardioprotective effect of MP was evaluated also using the in vivo heart model of I/R injury. We demonstrated that post-ischemic treatment with MP significantly attenuated the size of myocardial infarction and the serum level of CK-MB induced by in vivo I/R model. Taken together, our data suggest that MP could provide significant cardioprotection against the I/R injury, and the underlying mechanisms by which MP prevented the cardiomyocyte death might be mediated through the GPR40-activated PI3K/Akt signaling pathways. These findings suggest the potential applications of MP in the treatment of I/R-induced heart injury.

Cardioprotection; Free fatty acid receptor 1; Ischemia/reperfusion; Palmitic acid methyl ester.