Circadian Regulation of Metabolism: Commitment to Health and Diseases

Abstract

The circadian clock is a biological timekeeping system to govern temporal rhythms of the endocrine system and metabolism. The master pacemaker of biological rhythms is housed in the hypothalamic suprachiasmatic nucleus (SCN) where approximately 20,000 neurons exist and receive light stimulus as a predominant timed external cue (zeitgeber). The central SCN clock orchestrates molecular clock rhythms in peripheral tissues and coordinates circadian metabolic homeostasis at a systemic level. Accumulated evidence underscores an intertwined relationship between the circadian clock system and metabolism: the circadian clock provides daily dynamics of metabolic activity whereas the circadian clock activity is modulated by metabolic and epigenetic mechanisms. Disruption of circadian rhythms due to shift work and jet lag confounds the daily metabolic cycle, thereby increasing risks of various metabolic diseases, such as obesity and type 2 diabetes. Food intake serves as a powerful zeitgeber to entrain molecular clocks and circadian clock regulation of metabolic pathways, independently of light exposure to the SCN. Thus, the daily timing of food intake rather than the diet quantity and quality contributes to promoting health and preventing disease development through restoring circadian control of metabolic pathways. In this review, we discuss how the circadian clock dominates metabolic homeostasis and how chrononutritional strategies benefit metabolic health, summarizing the latest evidence from basic and translational studies.

Keywords: chrononutrition; circadian clock; gut microbiome; metabolic diseases; metabolism; multi-tissue communication.