Regulation of Myocardial Ketone Oxidative Proteins by Increased O-GlcNAcylation

An adult heart exhibits tremendous metabolic flexibility by utilizing a variety of substrates to meet its constant fuel demand. However, this metabolic flexibility is lost during overt diabetes. Moreover, heart mitochondria exhibit a low rate of ketone oxidation in type 1 diabetes. However, the mechanism of this reduction and regulation of the ketolytic pathway in a diabetic heart is incompletely understood. Recently, O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) to proteins has been recognized as a key glucose-induced posttranslational modification (PTM) in mediating the adverse effects of diabetes in the cardiovascular system. We therefore sought to test the hypothesis that modulation of transcriptional and/or posttranslational mechanisms via increased protein O-GlcNAcylation may induce regulatory changes in the myocardial ketolytic machinery in a diabetic heart. Our findings from the hearts of streptozotocin-induced diabetic mice confirmed that diabetes promotes significant (P < 0.05) transcri...