Linking the Cardiomyocyte Circadian Clock to Myocardial Metabolism

Abstract

The energetic demands imposed upon the heart vary dramatically over the course of the day. In the face of equally commanding oscillations in the neurohumoral mileu, the heart must respond both rapidly and appropriately to its diurnal environment, for the survival of the organism. A major response of the heart to alterations in workload, nutrients, and various neurohumoral stimuli is at the level of metabolism. Failure of the heart to achieve adequate metabolic adaptation results in contractile dysfunction. Substantial evidence is accumulating which suggests that a transcriptionally based timekeeping mechanism known as the circadian clock plays a role in mediating myocardial metabolic rhythms. Here, we provide an overview of our current knowledge regarding the interplay between the circadian clock within the cardiomyocyte and myocardial metabolism. This includes a particular focus on circadian clock mediated regulation of endogenous energy stores, as well as those mechanisms orchestrating circadian rhythms in metabolic gene expression. An essential need to elucidate fully the functions of this molecular mechanism in the heart remains.