Tick tock: how the body’s circadian clock keeps cardiometabolic rhythm in check

Abstract

The circadian clock orchestrates the internal timing of numerous physiological processes through an approximately 24-h cycle. It comprises a hypothalamic central clock, which responds to light cues and entrains peripheral clocks within individual cells and organs that, depending on the tissue, regulate gene expression across diverse biological functions in a tissue-specific manner. Peripheral clocks are also entrained by feeding and exercise-related cues, enabling their synchronization with feeding rhythm and physiology. Together, these clocks maintain a complex molecular network essential for metabolic homeostasis. Disruption of circadian rhythms, driven by genetic, environmental, or behavioral factors, is increasingly recognized as a major contributor to cardiometabolic disorders. Modern lifestyles, including shift work, irregular sleep, prolonged exposure to artificial light at night, jet lag, and erratic eating schedules, misalign circadian clocks with environmental cues, contributing to disruption of circadian rhythms or chronodisruption. This misalignment alters hormonal regulation, promotes systemic inflammation, and impairs metabolic balance, thereby increasing the risk of cardiovascular disease, obesity, type 2 diabetes, and related complications. The present review examines the mechanistic roles of core circadian clock genes in cardiometabolic health, highlighting their regulation of physiological processes in peripheral organs such as the heart, liver, and adipose tissue. We further discuss how circadian clock disruption accelerates disease onset and progression and explore emerging therapeutic strategies, including pharmacological modulation of the molecular circadian clock components and personalized chronotherapy. These approaches offer promising avenues to restore circadian alignment and mitigate cardiometabolic risk.