Circadian regulation of cardiac metabolism
Lilei Zhang, Mukesh K. Jain
Lilei Zhang, Mukesh K. Jain
Published August 2, 2021
Citation Information: J Clin Invest. 2021;131(15):e148276. https://doi.org/10.1172/JCI148276.
View: Text | PDF
Review Series

Circadian regulation of cardiac metabolism

Abstract

Circadian rhythm evolved to allow organisms to coordinate intrinsic physiological functions in anticipation of recurring environmental changes. The importance of this coordination is exemplified by the tight temporal control of cardiac metabolism. Levels of metabolites, metabolic flux, and response to nutrients all oscillate in a time-of-day–dependent fashion. While these rhythms are affected by oscillatory behavior (feeding/fasting, wake/sleep) and neurohormonal changes, recent data have unequivocally demonstrated an intrinsic circadian regulation at the tissue and cellular level. The circadian clock — through a network of a core clock, slave clock, and effectors — exerts intricate temporal control of cardiac metabolism, which is also integrated with environmental cues. The combined anticipation and adaptability that the circadian clock enables provide maximum advantage to cardiac function. Disruption of the circadian rhythm, or dyssynchrony, leads to cardiometabolic disorders seen not only in shift workers but in most individuals in modern society. In this Review, we describe current findings on rhythmic cardiac metabolism and discuss the intricate regulation of circadian rhythm and the consequences of rhythm disruption. An in-depth understanding of the circadian biology in cardiac metabolism is critical in translating preclinical findings from nocturnal-animal models as well as in developing novel chronotherapeutic strategies.

Authors

Lilei Zhang, Mukesh K. Jain

×

Figure 1

Basic concepts of circadian rhythm.

Options: View larger image (or click on image) Download as PowerPoint
Basic concepts of circadian rhythm. (A) The central clock exists in the ...
(A) The central clock exists in the suprachiasmatic nucleus (SCN) in the hypothalamus, receives optic input, and sends out neurohormonal signals to other peripheral tissues, such as the heart. The molecular clocks in the peripheral tissues (e.g., heart) are termed the peripheral clock; it receives entrainment signal both from the central clock and from additional external stimuli (e.g., diet and exercise). (B) The normal rhythm may be disrupted by a change in period, phase, or amplitude, or any combination of these. (C) The diurnal rhythm starts at zeitgeber time (ZT) 0, which is defined by the turning on of the light. In the light phase, diurnal animals (including humans) are active and nocturnal animals are resting. The opposite happens in the dark phase. When we refer to the active versus resting phases, we are describing the same biological phase and processes for any species studied.