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Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis

Grant, L.K., Ftouni, S., Nijagal, B., De Souza, D.P., Tull, D., McConville, M.J., Rajaratnam, S.M.W., Lockley, S.W. and Anderson, C. (2019) Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis Scientific Reports, 9 (1).

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Abstract

Establishing circadian and wake-dependent changes in the human metabolome are critical for understanding and treating human diseases due to circadian misalignment or extended wake. Here, we assessed endogenous circadian rhythms and wake-dependent changes in plasma metabolites in 13 participants (4 females) studied during 40-hours of wakefulness. Four-hourly plasma samples were analyzed by hydrophilic interaction liquid chromatography (HILIC)-LC-MS for 1,740 metabolite signals. Group-averaged (relative to DLMO) and individual participant metabolite profiles were fitted with a combined cosinor and linear regression model. In group-level analyses, 22% of metabolites were rhythmic and 8% were linear, whereas in individual-level analyses, 14% of profiles were rhythmic and 4% were linear. We observed metabolites that were significant at the group-level but not significant in a single individual, and metabolites that were significant in approximately half of individuals but not group-significant. Of the group-rhythmic and group-linear metabolites, only 7% and 12% were also significantly rhythmic or linear, respectively, in �50% of participants. Owing to large inter-individual variation in rhythm timing and the magnitude and direction of linear change, acrophase and slope estimates also differed between group- and individual-level analyses. These preliminary findings have important implications for biomarker development and understanding of sleep and circadian regulation of metabolism. © 2019, The Author(s).

Item Type: Article
Authors :
NameEmailORCID
Grant, L.K.
Ftouni, S.
Nijagal, B.
De Souza, D.P.
Tull, D.
McConville, M.J.
Rajaratnam, S.M.W.
Lockley, S.W.s.lockley@surrey.ac.uk
Anderson, C.
Date : 2019
DOI : 10.1038/s41598-019-40353-8
Depositing User : Clive Harris
Date Deposited : 17 Jun 2020 00:37
Last Modified : 17 Jun 2020 00:37
URI: http://epubs.surrey.ac.uk/id/eprint/857809

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