Laurent Bultot, IREC, Brussels, Belgium

Post-doctoral researcher, Pole of Cardiovascular Research (CARD), UCLouvain, Institute of Clinical and Experimental Research (IREC), Brussels, Belgium

Abstract

Cardiac metabolic flexibility expresses the heart capacity to adapt its metabolism according to substrate availability, switching notably from fatty acid to glucose oxidation after a meal. This metabolic flexibility is recognized to be important for accurate cardiac function. In a diabetic’s heart, glucose utilisation is abrogated inducing metabolic inflexibility and cardiac dysfunction leading finally to cardiomyopathy. The loss of this metabolic flexibility results, at least in part, of insulin incapacity to promote translocation of the glucose transporter GLUT4 to the plasma membrane. Recently, our laboratory has demonstrated that leucine and ketones bodies (KBs), two early markers of diabetes, induce a disruption of GLUT4 translocation in response to insulin via a global rise in protein acetylation. This increase of acetylation is resulting from an accumulation of acetyl-CoA, the acetyl donor necessary to the acetylation process and a by-product of leucine and KB catabolism. Circulating fatty acids, like leucine and ketones bodies, are increased in pre-diabetic patients and are largely described to be involved in the onset of cardiac metabolic inflexibility. Metabolism of fatty acids also leads to acetyl-CoA accumulation. Therefore, the aim of the present works is to evaluate the role of acetyl-CoA and protein acetylation in the development of cardiac insulin-resistance in response to fatty acids.