Cardiac Energy Metabolism in Heart Failure Associated with Obesity and Diabetes

Abstract

Obesity and diabetes are important risk factors for the development of heart failure. The metabolic abnormalities that accompany obesity and diabetes result in dramatic alterations in cardiac energy metabolism, which can contribute to the progression of heart failure. Elevated rates of fatty acid oxidation and depressed rates of glucose oxidation characterize the cardiac metabolic profile in the setting of obesity-induced insulin resistance and diabetes. This metabolic profile results in a marked cardiac insulin resistance, which is accompanied by decrements in both cardiac function and efficiency, and by the accumulation of potentially toxic fatty acid metabolites in the heart. Acetylation of various mitochondrial and glycolytic enzymes are altered in obesity and diabetes, which may also contribute to the pathogenesis of heart failure in obesity and diabetes. As a result, therapeutic interventions that prevent or reverse the energy metabolic switch in the heart of obese and diabetic individuals, and/or the accumulation of fatty acid metabolites may lessen the severity of heart failure. These interventions include inhibiting myocardial fatty acid oxidation, stimulating glucose oxidation, restoring myocardial insulin sensitivity, preventing myocardial fatty acid metabolite accumulation, and inhibiting the acetylation of key enzymes involved in fatty acid oxidation. This paper reviews the metabolic alterations that occur in heart failure associated with obesity and diabetes, and the molecular mechanisms responsible for these changes.