Nutrients, Clock Genes, and Chrononutrition

Abstract

Circadian clocks that comprise clock genes exist throughout the body and control daily physiological events. The central clock that dominates activity rhythms is entrained by light/dark cycles, whereas peripheral clocks regulating local metabolic rhythms are determined by feeding/fasting cycles. Nutrients reset peripheral circadian clocks and the local clock genes control downstream metabolic processes. Metabolic states also affect the clockworks in feedback manners. Because the circadian system organizes whole energy homeostasis, including food intake, fat accumulation, and caloric expenditure, the disruption of circadian clocks leads to metabolic disorders. Recent findings show that time-restricted feeding during the active phase amplifies circadian clocks and improves metabolic disorders induced by a high-fat diet without caloric reduction, whereas unusual/irregular food intake induces various metabolic dysfunctions. Such evidence from nutrition studies that consider circadian system (chrononutrition) has rapidly accumulated. We review molecular relationships between circadian clocks and nutrition as well as recent chrononutrition findings.

Keywords: Breakfast; Chrononutrition; Circadian clocks; Circadian rhythm; Clock genes; High-fat diet; Meal timing; Metabolic disorders; Nutrition.

Fig. 1

Schematic representation of the circadian clock system and chrononutrition. Light/dark cycles entrain the central clock in the suprachiasmatic nucleus (SCN) dominating activity rhythms, whereas feeding cues determine the phase of peripheral clocks that dominate local metabolic rhythms. Both nutrients and meal timing can affect the clock system, thus “chrononutrition” has two aspects: 1) nutrients/food components regulate the clock system, e.g., caffeine prolongs the period of circadian clocks and the locomotor activity rhythm, and high-fat diets alter the rhythms of lipogenesis, circulating lipids, locomotor activity, and feeding behavior; 2) meal-timing affects output of the clock system, e.g., skipping breakfast and nocturnal eating increases risk of obesity, whereas time-restricted feedings prevent metabolic disorders induced by high-fat diets. Regular/time-restricted feedings synchronize and amplify the rhythms of clock system, whereas irregular/unusual feedings cause desynchronization and attenuate the rhythms, probably leading to metabolic disorders