title: Effect of sleep deprivation on the human metabolome.
abstract: Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics approach. Here we have used untargeted and targeted liquid chromatography (LC)/MS metabolomics to examine the effect of acute sleep deprivation on plasma metabolite rhythms. Twelve healthy young male subjects remained in controlled laboratory conditions with respect to environmental light, sleep, meals, and posture during a 24-h wake/sleep cycle, followed by 24 h of wakefulness. Two-hourly plasma samples collected over the 48 h period were analyzed by LC/MS. Principal component analysis revealed a clear time of day variation with a significant cosine fit during the wake/sleep cycle and during 24 h of wakefulness in untargeted and targeted analysis. Of 171 metabolites quantified, daily rhythms were observed in the majority (n = 109), with 78 of these maintaining their rhythmicity during 24 h of wakefulness, most with reduced amplitude (n = 66). During sleep deprivation, 27 metabolites (tryptophan, serotonin, taurine, 8 acylcarnitines, 13 glycerophospholipids, and 3 sphingolipids) exhibited significantly increased levels compared with during sleep. The increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of acute sleep deprivation and deserve further study. This report, to our knowledge the first of metabolic profiling during sleep and sleep deprivation and characterization of 24 h rhythms under these conditions, offers a novel view of human sleep/wake regulation.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Davies
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London SM2 5NG, United Kingdom; and.
authors.forename: Joo Ern
authors.initials: JE
authors.lastname: Ang
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Revell
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Ben
authors.initials: B
authors.lastname: Holmes
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Anuska
authors.initials: A
authors.lastname: Mann
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Francesca P
authors.initials: FP
authors.lastname: Robertson
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Nanyi
authors.initials: N
authors.lastname: Cui
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Benita
authors.initials: B
authors.lastname: Middleton
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ackermann
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Thumser
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London SM2 5NG, United Kingdom; and.
authors.forename: Florence I
authors.initials: FI
authors.lastname: Raynaud
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom; d.skene@surrey.ac.uk.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Skene
mesh_terms: D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D012892:Sleep Deprivation / Q000097:blood / Q000378:metabolism*
keywords: biomarker; circadian rhythms; depression; melatonin; total sleep deprivation