The quality and quantity of nutrition are well-accepted determinants of health. On the other hand, endogenous circadian clock governs daily nutritional rhythms such as nutrient digestion, absorption, and metabolism, which are coordinated by behavioral rhythms such as activity-rest and feeding-fasting cycles. Therefore, circadian rhythm disruption causes various physiological impairments such as sleep disorders and metabolic diseases. Chrono-nutrition is the research field that studies the time-of-day effect of food intake on health and that develops the functional food that improves circadian rhythms of physical performance. In the present review, I have tried to summarize the recent studies on the effectiveness of time-restricted feeding on the prevention and improvement of metabolic diseases, such as diabetes and obesity.

One of the characteristics of diabetic patients in recent years is the increase in the body weight. The reasons for the rapid increase in obesity and the number of patients with lifestyle-related diseases are diverse and include energy intake from fatty foods, lack of exercise, excessive stress, etc. Interestingly, a negative correlation between the number of diabetics and the number of people who go to bed at 10:00 p.m. was observed, suggesting that the shift to a nighttime lifestyle may be a factor in the development of lifestyle-related diseases. This shift in the time of day is expected to have a strong impact on the circadian rhythm of biological functions. The circadian rhythm of biological functions is a mechanism that has been conserved throughout evolution and is precisely controlled by the clock genes. It has long been known that the onset of disease has a specific onset time, but recently there have been a series of reports suggesting the involvement of clock genes in the onset of lifestyle-related diseases, especially metabolic diseases such as metabolic syndrome. In this article, we will discuss the relationship between circadian rhythm abnormalities and metabolic diseases from the viewpoint of clock genes.

Plasma phosphate levels are maintained mainly by intestinal absorption, bone metabolism (bone formation and resorption), renal excretion and reabsorption, and tissue transfer to soft tissues such as liver and muscle. Plasma phosphate concentration forms a diurnal rhythm, and the mechanism of its formation is considered to be an important factor in defining the phosphate concentration during early morning fasting. The risk of death in CKD (Chronic kidney disease) and maintenance dialysis patients is known to be positively correlated with early morning fasting plasma phosphate concentration.

Recently, it was shown that the Nampt (nicotinamide phosphoribosyl transferase)/NAD (nicotinamide adenine dinucleotide) system regulates the expression levels of the sodium-dependent phosphate transporters NaPi-IIa (Npt2a), NaPi-IIc (Npt2c), and NaPi-IIb (Npt2b). This mechanism is involved in the formation of diurnal rhythms in plasma phosphate levels. In fact, the diurnal rhythm of plasma phosphate concentration is abolished in Nampt heterozygous mice.

In addition, liver-specific Nampt-deficient mice show abnormal diurnal rhythm formation, suggesting that the Nampt/NAD system may also be involved in the tissue transfer of phosphate. Further understanding of the formation of diurnal rhythms in plasma phosphate concentration is important for phosphate management in CKD and maintenance dialysis patients.