Circadian rhythms in cardiac metabolic flexibility

Abstract

Numerous aspects of cardiovascular physiology (e.g., heart rate, blood pressure) and pathology (e.g., myocardial infarction and sudden cardiac death) exhibit time-of-day-dependency. In association with day-night differences in energetic demand and substrate availability, the healthy heart displays remarkable metabolic flexibility through temporal partitioning of the metabolic fate of common substrates (glucose, lipid, amino acids). The purpose of this review is to highlight the contribution that circadian clocks provide toward 24-hr fluctuations in cardiac metabolism and to discuss whether attenuation and/or augmentation of these metabolic rhythms through adjustment of nutrient intake timing impacts cardiovascular disease development.

Keywords: Circadian; heart; metabolism; nutrients.

Figure 1.. Temporal partitioning of myocardial glucose metabolism.

At the beginning of the active period (i.e., breakfast time), AMP-activated protein kinase (AMPK) promotes glucose uptake, glycolysis, and the hexosamine biosynthetic pathway, as well as full oxidation via pyruvate dehydrogenase (PDH). At the end of the active period (i.e., dinner time), decreased levels of inhibitor-1 promotes protein phosphatase 1 (PP1) activity, and concomitant storage of excess glucose as glycogen (which can serve as a fuel source during the upcoming sleep period).

Figure 2.. The metabolic fate of lipids in the heart is time-of-day-dependent.

At the beginning of the active period (i.e., breakfast time), increased lipoprotein lipase (LPL) activity promotes lipo-protein-derived fatty acid uptake and oxidation; resultant acetyl-CoA can serve as a substrate in protein acetylation (Ac) reactions. At the end of the active period (i.e., dinner time), fatty acids are channeled into triglyceride synthesis (which can serve as a fuel and/or source for lipid signaling molecules during the upcoming sleep period).

Figure 3.. Amino acids selectively augment cellular consistent turnover at the beginning of the sleep phase.

At the beginning of the active period (i.e., breakfast time), the heart utilizes amino acids for basal processes. In contrast, at the end of the active period (i.e., dinner time), a concomitant increase in mTOR signaling activation, ribosomal RNA, and amino acid content, augments protein synthesis (and growth/repair).