Reciprocal Interactions between Circadian Clocks, Food Intake, and Energy Metabolism

SIMPLE SUMMARY: Our daily life follows 24-h cycles in various biological functions, such as sleep–wake and feeding/fasting cycles. These rhythms are regulated by endogenous clocks that are synchronized by environmental cues. In mammals, the main circadian clock is located in the suprachiasmatic nuclei at the basis of the brain and can be reset by ambient light, be it natural or artificial. Many secondary clocks, located in the various brain areas and peripheral organs, are regulated by the main circadian clock via the autonomic nervous system, hormonal secretions, and also by meal times. Numerous studies have underlined the importance of circadian rhythmicity for good metabolic health. Moreover, circadian disruption has a negative impact on metabolism, with increased metabolic risks, such as obesity and diabetes. Based on research with animal models and clinical and epidemiological studies in humans, some mechanistic insights are given to explain why circadian disruption, such as exposure to bright light at night or nocturnal meals, can have detrimental effects on energy balance in humans, and how timed nutrition and sleep may counteract or limit these adverse health effects. ABSTRACT: Like other biological functions, food intake and energy metabolism display daily rhythms controlled by the circadian timing system that comprises a main circadian clock and numerous secondary clocks in the brain and peripheral tissues. Each secondary circadian clock delivers local temporal cues based on intracellular transcriptional and translational feedback loops that are tightly interconnected to intracellular nutrient-sensing pathways. Genetic impairment of molecular clocks and alteration in the rhythmic synchronizing cues, such as ambient light at night or mistimed meals, lead to circadian disruption that, in turn, negatively impacts metabolic health. Not all circadian clocks are sensitive to the same synchronizing signals. The master clock in the suprachiasmatic nuclei of the hypothalamus is mostly synchronized by ambient light and, to a lesser extent, by behavioral cues coupled to arousal and exercise. Secondary clocks are generally phase-shifted by timed metabolic cues associated with feeding, exercise, and changes in temperature. Furthermore, both the master and secondary clocks are modulated by calorie restriction and high-fat feeding. Taking into account the regularity of daily meals, the duration of eating periods, chronotype, and sex, chrononutritional strategies may be useful for improving the robustness of daily rhythmicity and maintaining or even restoring the appropriate energy balance.