Abstract

Circadian rhythms are biological rhythms with a period of around 24 hours. In this study, we compared the metabolome of the liver of medaka during the day and night. To comprehensively analyze the circadian variations in the levels of metabolites in the liver, livers were isolated from Zeitgeber time (ZT)4 and ZT16, and the variations in metabolite levels were evaluated. Inosinemonophosphate (IMP) and uridinemonophosphate (UMP) were found to be increased at night, indicating that nucleotide synthesis is most active during the night. Furthermore, the levels of metabolites of the tricarboxylic acid cycle were also reduced at night. In addition, the levels of many amino acids were reduced during the night, suggesting that the amino acids had been degraded. Moreover, the citrulline/ornithine ratio, which is related to arginine consumption, was lower during the day than at night. This pattern suggests that the urea cycle is activated during the day, whereas large amounts of nitric oxide and citrulline may be produced from arginine via nitric oxide synthase during the night. The results of this metabolomic analysis may be useful in future fundamental research to provide insight into chronobiology as well as applied research on drug evaluations using medaka as a model species.

Highlights

  • Many organisms display functions with a biological rhythm over a period of approximately 24 hours, which is known as the circadian rhythm; these physiological function include sleeping and waking, hormone secretion, and the regulation of blood pressure and temperature

  • Analysis of metabolites related to purine and pyrimidine metabolism revealed an increase in monophosphates at night, including 3′ -cytidine monophosphate (CMP; day-to-night ratio = 1.8), uridine monophosphate (UMP; ratio = 1.3), guanosine monophosphate (GMP; ratio = 1.3), and inosine monophosphate (IMP; ratio = 2.6) (Fig. 3)

  • A coupling of metabolism and the circadian rhythm has been established in various organisms from humans to yeast

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Summary

Introduction

Many organisms display functions with a biological rhythm over a period of approximately 24 hours, which is known as the circadian rhythm; these physiological function include sleeping and waking, hormone secretion, and the regulation of blood pressure and temperature. They developed a computational method to integrate both circadian gene expression and metabolic network metabolomics analysis, and reported that the level of IMP, an intermediate metabolite in de novo purine synthesis, showed significant circadian oscillation in larval zebrafish[7]. Analysis of metabolites related to purine and pyrimidine metabolism revealed an increase in monophosphates at night, including 3′ -cytidine monophosphate (CMP; day-to-night ratio = 1.8), uridine monophosphate (UMP; ratio = 1.3), guanosine monophosphate (GMP; ratio = 1.3), and inosine monophosphate (IMP; ratio = 2.6) (Fig. 3).

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