Life on earth proceeds with daily cyclic changes in circumstances. Plants conduct photosynthesis during the daytime, and nocturnal animals forage for food at night. Many living organisms have developed intrinsic 24-h cycles called circadian clocks that enable the expression of activities at appropriate times. The molecular mechanisms of clocks have been investigated in detail since the first clock mutant was isolated from fruit flies [1]. Several clock genes are homologous from flies to mammals and thus circadian clock systems in all vertebrates have the same origin, whereas plants, fungi, and protists have developed other circadian systems [2]. Regardless of the molecular bases, transcriptional-translational feedback loops play critical roles in the generation or maintenance of circadian rhythms. The main feedback loop in mammals comprises several core clock genes, including Bmal1, Clock, Per1/2, and Cry1/2 [3]. In addition to these, other clock genes or clock-controlled genes, such as Rev-erbα/β, Rorα/β, Dbp, Dec1/2, CK1ε/δ, and NPAS2 cooperate to sustain mammalian circadian clocks. Genome-wide transcriptome and ChIP-seq analyses have shown that clock genes control the transcription of thousands of genes with chromatin remodeling [4–6]. Notably, posttranscriptional regulation plays a substantial role in controlling circadian mRNA expression [4]. The circadian control of transcribed genes leads to rhythmic physiological events.

Light/dark cycles entrain the central clock in the suprachiasmatic nucleus (SCN) that is located in the hypothalamus where it mainly dominates activity-related rhythms, such as sleep/wake cycles, the autonomic nervous system, core body temperature, and melatonin secretion. In contrast, feeding/fasting cycles entrain peripheral clocks that are located in most tissues including even part of the brain [7•]. Peripheral clocks dominate local physiological processes, including glucose and lipid homeostasis, hormonal secretion, xenobiotics, the immune response, and the digestion system [8]. As the central clock organizes local clocks through neuronal and humoral signals, desynchronization among clocks is believed to result in the development of unpreferable conditions, such as metabolic disorders, cancer, and psychiatric disorders [9].

Circadian clocks enable the anticipation of daily events, conferring a considerable advantage for saving time and the efficient use of energy. The central clock activates the sympathetic nervous system and increases body temperature and blood pressure ahead of the active phase, facilitating the start of activities. Digestion/absorption systems also prepare before breakfast based on the time of local clocks [7•, 10]. Because colonic motility also is regulated by the local clocks, gastrointestinal symptoms are prevalent among shift workers and time-zone travelers [11]. In addition to local physiological events in tissues, some activity rhythms also are affected by feeding. Scheduled feeding elicits food anticipatory activity that is independent of light/dark cues and is perceived as food-seeking behavior approximately 2 hours before feeding [7•, 12]. This activity rhythm persists in rodents with SCN lesions, indicating that the central clock is not essential for food anticipatory activity. Because food available timing can be occasionally restricted in the wild, circadian anticipatory control of behavior and energy metabolism probably increases food usage and energy efficiency. Indeed, many studies have shown that circadian clocks intimately control energy metabolism [13]. Many genes associated with glucose and lipid homeostasis, especially those encoding rate limiting enzymes in various metabolic processes, are under circadian control. Thus, mutations or deletions of clock genes lead to metabolic disorders [14]. Mice with mutant Clock have attenuated feeding rhythm, hyperphagic, and obesity as well as altered gluconeogenesis, insulin insensitivities, and lipid homeostasis [15, 16]. Glucose and lipid homeostasis are similarly impaired in Bmal1 knockout mice [17, 18], and altered lipid metabolism, attenuated nocturnal food intake with total overeating, and developing significant obesity on high-fat diet are reported in Per2 knockout mice [19, 20]. A few studies have suggested an association between genetic variance in clock genes and metabolic risk in humans [14, 21•]. In addition, an epigenetic state of clock genes might be associated with obesity [22]. These genetic associations indicate mutual interaction among circadian clocks, metabolism, and nutrition.

Recently, a novel field between nutrition and circadian clock system is referred as “chrononutrition” [7•, 10] (Fig. 1). In this article, we review recent findings regarding chrononutrition, food components that regulate circadian clocks, and meal times that affect metabolic homeostasis.