Diurnal variation of metabolites in three individual participants

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.

KEYWORDS:

• Circadian rhythm
• diurnal
• metabolomics
• metabolites

Declaration of Interest Statement

The authors declare no relevant conflicts of interest.

Supplementary Material

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Additional information

Funding

This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute. EBK was supported by NIH K24HL105664, R01HL114088, R01GM105018, R01HL128538, P01AG009975. FG was also supported by Roswell Park Cancer Institute and Cancer Center Supporting Grant P30CA016056. In addition, the experimental work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center National Center for Advancing Translational Sciences, National Institutes of Health Award UL [1TR002541] and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health; Division of Cancer Epidemiology and Genetics, National Cancer Institute [Intramural Research Program].