title: Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation.
abstract: Understanding how metabolite levels change over the 24 hour day is of crucial importance for clinical and epidemiological studies. Additionally, the association between sleep deprivation and metabolic disorders such as diabetes and obesity requires investigation into the links between sleep and metabolism. Here, we characterise time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles. Healthy male participants (n = 15) completed an in-laboratory study comprising one 24 h sleep/wake cycle prior to 24 h of continual wakefulness under highly controlled environmental conditions. Urine samples were collected over set 2-8 h intervals and analysed by (1)H NMR spectroscopy. Significant changes were observed with respect to both time of day and sleep deprivation. Of 32 identified metabolites, 7 (22%) exhibited cosine rhythmicity over at least one 24 h period; 5 exhibiting a cosine rhythm on both days. Eight metabolites significantly increased during sleep deprivation compared with sleep (taurine, formate, citrate, 3-indoxyl sulfate, carnitine, 3-hydroxyisobutyrate, TMAO and acetate) and 8 significantly decreased (dimethylamine, 4-DTA, creatinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 4-DEA, 4-hydroxyphenylacetate). These data indicate that sampling time, the presence or absence of sleep and the response to sleep deprivation are highly relevant when identifying biomarkers in urinary metabolic profiling studies.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.|St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Guro F
authors.initials: GF
authors.lastname: Giskeødegård
authors.affiliation: Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Davies
authors.affiliation: Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Revell
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Hector
authors.initials: H
authors.lastname: Keun
authors.affiliation: Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Skene
mesh_terms: D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D002951:Citrates / Q000652:urine; D003404:Creatinine / Q000652:urine; D004123:Dimethylamines / Q000652:urine; D005561:Formates / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology* / Q000652:urine*; D013654:Taurine / Q000652:urine; D013997:Time Factors; D055815:Young Adult
chemical_list: D002951:Citrates; D004123:Dimethylamines; D005561:Formates; D013654:Taurine; C034516:dimethylamine; D003404:Creatinine