Elsevier

Frontiers in Neuroendocrinology

Volume 28, Issues 2–3, August–September 2007, Pages 61-71
Frontiers in Neuroendocrinology

Review
The relationship between nutrition and circadian rhythms in mammals

https://doi.org/10.1016/j.yfrne.2007.03.001Get rights and content

Abstract

The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus regulates circadian rhythms in mammals. The clock is an intracellular, transcriptional mechanism sharing the same molecular components in SCN neurons and in peripheral cells, such as the liver, intestine, and retina. The circadian clock controls food processing and energy homeostasis by regulating the expression and/or activity of enzymes involved in cholesterol, amino acid, lipid, glycogen, and glucose metabolism. In addition, many hormones involved in metabolism, such as insulin, glucagon, adiponectin, corticosterone, leptin, and ghrelin, exhibit circadian oscillation. Furthermore, disruption of circadian rhythms is involved in the development of cancer, metabolic syndrome, and obesity. Metabolism and food intake also feed back to influence the biological clock. Calorie restriction (CR) entrains the SCN clock, whereas timed meals entrain peripheral oscillators. Furthermore, the cellular redox state, dictated by food metabolism, and several nutrients, such as glucose, ethanol, adenosine, caffeine, thiamine, and retinoic acid, can phase-shift circadian rhythms. In conclusion, there is a large body of evidence that links feeding regimens, food components, and the biological clock.

Introduction

The rotation of earth around its axis imparts light and dark cycles of 24 h. Organisms on earth developed the ability to predict these cycles and evolved to restrict their activity to the night or day. By developing an endogenous circadian (circa—about and dies—day) clock, which is entrained to external time cues, animals and plants ensure that physiological processes are carried out at the appropriate, optimal time of day or night [103]. In mammals, the circadian clock influences nearly all aspects of physiology and behavior, including sleep–wake cycles, cardiovascular activity, endocrine system, body temperature, renal activity, physiology of the gastrointestinal tract, hepatic metabolism, etc. [103], [109]. Disruption of circadian coordination may be manifested by hormone imbalance, psychological and sleep disorders, cancer proneness, and reduced life span [31], [40], [48], [70], [105], [109]. In contrast, resetting of circadian rhythms has led to well-being and increased longevity [61], [65], [67].

The control of the biological clock over feeding behavior has been well established. In addition, molecularly, the biological clock regulates the expression and/or activity of enzymes and hormones involved in metabolism. However, recently, there is a growing body of evidence that metabolism, food consumption, timed meals, and some nutrients feed back to entrain the clock. This review will summarize the recent findings concerning the relationship between feeding regimens, food components, metabolism, and circadian rhythms.

Section snippets

The mammalian biological clock

In mammals, the central circadian clock is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain. The SCN clock is composed of multiple, single-cell circadian oscillators, which, when synchronized, generate coordinated circadian outputs that regulate overt rhythms [56], [84], [108], [146]. Similar clock oscillators have been found in peripheral tissues, such as the liver, intestine, and retina. Thus, the central circadian clock (often termed the master clock) is

The biological clock at the molecular level

Transcriptional–translational feedback loops lie at the very heart of the core clock mechanism of animals, plants, and fungi. Generation of circadian rhythms is dependent on the concerted co-expression of specific clock genes. Genetic analysis of mutations affecting the clock in organisms, such as Neurospora, Drosophila, Cyanobacteria, Arabidopsis, and, most recently, the mouse, have paved the way for the identification of these clock genes. In mammals, the clock is an intracellular,

Effect of the biological clock on metabolism

The fraction of cyclically expressed transcripts in each peripheral tissue ranges between 5% and 10% of the total population and the vast majority of these genes are tissue-specific [3], [34], [71], [103], [124], [137]. Many hormones involved in metabolism, such as insulin [76], glucagon [116], adiponectin [4], corticosterone [32], leptin, and ghrelin [11], have been shown to exhibit circadian oscillation. In addition to the endocrine control, the circadian clock has been reported to regulate

Circadian rhythms and metabolic disorders

Recent studies have suggested that disruption of circadian rhythms in the SCN and peripheral tissues may lead to manifestations of the metabolic syndrome [13], [14], [132]. Shift work [66] and sleep deprivation [125] have been shown to be associated with increased adiposity, findings that have been linked to the sleep-associated peak in leptin secretion [128]. In mice, a high-fat diet led to a mild metabolic syndrome of obesity, hyperlipidemia, and hyperglycemia, but had minimal effects on the

Timed meals and circadian rhythms

Similarly to the control of the circadian clock on metabolism, food is a very potent synchronizer (zeitgeber) for peripheral clocks. Recent evidence indicates that clock gene expression in the liver and other peripheral tissues is entrained to periodic meals [135]. Limiting the time and duration of food availability with no calorie reduction is termed restricted feeding (RF) [16], [59], [124]. Animals, which receive food ad libitum everyday at the same time for only a few hours, adjust to the

Circadian rhythms and caloric restriction

Calorie restriction (CR) refers to a dietary regimen low in calories without malnutrition. CR restricts the amount of calories derived from carbohydrates, fats, or proteins to 25–60% below that of control animals fed ad libitum [86]. It has been documented that calorie restriction significantly extends the life span of rodents by up to 50% [72], [87]. In addition to the increase in life span, CR also delays the occurrence of age-associated pathophysiological changes, such as cancer, diabetes,

Effect of metabolism and food components on circadian rhythms

Recent experiments have suggested a direct route through which food may influence peripheral clocks [117]. CLOCK and its homolog NPAS2 can bind efficiently to BMAL1 and consequently to their E-box sequences in the presence of reduced nicotinamide adenine dinucleotides (NADH and NADPH). On the other hand, the oxidized forms of the nicotinamide adenine dinucleotides (NAD+ and NADP+) inhibit DNA binding of CLOCK:BMAL1 or NPAS2:BMAL1 [117], [118]. The NAD(P) redox equilibrium depends on the

Concluding remarks

The prominent influence of the circadian clock on human physiology is demonstrated by the temporal and pronounced activity of a plethora of systems, such as sleep and wake cycles, feeding behavior, metabolism, physiological and endocrine activity. Disrupted biological rhythms lead to attenuated circadian feeding rhythms, hyperphagia, obesity, cancer proneness, and reduced life expectancy. As food components and feeding time have the ability to reset bodily rhythms, it is of extreme importance

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