4.8 Review

Circadian regulation of cardiac metabolism

Journal

JOURNAL OF CLINICAL INVESTIGATION
Volume 131, Issue 15, Pages -

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI148276

Keywords

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Funding

  1. National Heart, Lung, and Blood Institute [K08HL123551, R01HL143067, R35HL135789, R01HL086548]
  2. American Heart Association-Allen Frontiers Award
  3. NIH [R01DK111478]
  4. Leducq Foundation Transatlantic Network of Excellence

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The circadian rhythm allows organisms to coordinate physiological functions in anticipation of environmental changes. The disruption of this rhythm leads to cardiometabolic disorders, affecting not only shift workers but also most individuals in modern society. Understanding circadian biology in cardiac metabolism is essential for developing novel chronotherapeutic strategies.
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.

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