Ketone Body Exposure of Cardiomyocytes Impairs Insulin Sensitivity and Contractile Function through Vacuolar-Type H(+)-ATPase Disassembly-Rescue by Specific Amino Acid Supplementation

This laboratory study tested the effect of ketone bodies on v-ATPase assembly and lipid uptake in rodent and human cardiomyocytes. Exposure to 3-beta-hydroxybutyrate induced v-ATPase disassembly and the cascade of events leading to contractile dysfunction and insulin resistance, similar to lipid oversupply. Acetoacetate did not induce v-ATPase dysfunction, and the negative effects of 3-beta-hydroxybutyrate were prevented by adding specific amino acids. The authors conclude ketone bodies should be used with caution in sedentary or prediabetic subjects because of possible aggravation of cardiac insulin resistance.