human circadian metabolome

The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transc...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 109; no. 7; pp. 2625 - 2629
Main Authors Dallmann, Robert, Viola, Antoine U, Tarokh, Leila, Cajochen, Christian, Brown, Steven A
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 14.02.2012
National Acad Sciences
Subjects
Amino acid metabolism
Amino acids
biochemical pathways
Biological Sciences
Biomarkers
Blood plasma
Circadian Rhythm
Circadian rhythms
Energy metabolism
Fatty acids
Food intake
human physiology
Human subjects
Humans
Light
Lipid metabolism
Metabolic disorders
metabolic syndrome
Metabolism
Metabolites
Metabolome
Mice
Plasma
Saliva
Saliva - metabolism
sleep
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Summary:The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest–activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ∼15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.
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Author contributions: R.D., A.U.V., C.C., and S.A.B. designed research; R.D. and A.U.V. performed research; R.D., A.U.V., L.T., and S.A.B. analyzed data; and R.D., L.T., and S.A.B. wrote the paper.
Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 4, 2012 (received for review September 1, 2011)
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1114410109