Abstract
The circadian system influences virtually all biological functions. Understanding the impact of circadian variation on metabolism may provide insight into mechanisms of circadian-associated disorders and guide the implementation of chrono-therapy. Previous research has reported circadian variation in 7-20% of metabolites in human blood. In this study, untargeted metabolomics profiles were measured using blood of two healthy men and one healthy woman, collected every 2 h for up to 48 h under carefully controlled conditions. The pattern of variation of each metabolite over time was examined on each participant separately, using both one- and two-order harmonic models. A total of 100 of 663 metabolites, representing all metabolite categories, showed diurnal rhythmic concentrations that exceeded the Bonferroni threshold (P < 2.5 × 10(-5)). Overall, peak times of many metabolites were clustered during the afternoon-midnight, including the majority of amino acids, all peptides, all lysolipids and all phospholipids, whereas the majority of steroids peaked in the morning. We observed substantial inter-individual variation for both peak times and amplitudes in these three subjects. In conclusion, at least 15% of blood metabolites, representing a broad group of biological pathways, exhibit diurnal variation in three participants. The average peak times of most of these metabolites are clustered in morning or afternoon-midnight. Further work is needed to validate and extend this work in more individuals.