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


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.

SUBMITTER: Grant LK 

PROVIDER: S-EPMC6418225 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Grant Leilah K LK   Ftouni Suzanne S   Nijagal Brunda B   De Souza David P DP   Tull Dedreia D   McConville Malcolm J MJ   Rajaratnam Shantha M W SMW   Lockley Steven W SW   Anderson Clare C  

Scientific reports 20190314 1


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 (re  ...[more]

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