Cardiac Metabolism and Energetic Control

Abstract

Cardiomyocytes are incessantly contracting; thus, they also require a continuous energy supply to fuel an optimal function. Fatty acids are the predominant substrate used in the adult heart for ATP production. However, the heart is metabolically versatile in using other substrates such as glucose, lactate, amino acids and ketone bodies when they become abundantly available. In addition to this versatile substrate utilization, complex regulatory mechanisms such as transcriptional regulation and post-translational modifications of key metabolic protein as well as allosteric regulation by metabolites or substrates within the metabolic network contribute to the metabolic flexibility of the heart. This flexibility confers the advantage of adequately supplying ATP in response to a variety of physiological conditions including developmental or nutritional changes. However, the failing heart is characterized by an energetic deficit and a loss of metabolic flexibility. Here, we will summarize typical metabolic features of the healthy heart, the foetal heart, the hypertrophied or failing heart, the aged heart and the obese or diabetic heart. In addition, strategies used as metabolic therapies in heart failure as well as the impact of well-established heart failure therapeutics on cardiac metabolism will be discussed.