Effect of sleep deprivation on the human metabolome
Open accessAbstract
Significance: Sleep restriction and circadian clock disruption are associated with metabolic disorders including obesity and diabetes; this association can be studied by using the powerful tool of metabolomics. By using liquid chromatography/MS metabolomics, we have characterized plasma metabolites that were significantly affected by acute sleep deprivation (mainly lipids and acylcarnitines), all increasing during sleep deprivation. Observed increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of sleep deprivation and deserve further study. Clear daily rhythms were observed in most metabolites, with 24 h wakefulness mainly reducing the amplitude of these rhythms. Our results further the understanding of sleep/wake regulation and the associated metabolic processes, and will be vital when using metabolic profiling to identify robust biomarkers for disease states and drug efficacy.
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In the acute SR study, only increases in lipid levels were observed after the deprivation period, while in the partial SR study also declines were recorded.
“In the acute SR study22, only increases in lipid levels were observed after the deprivation period, while in the partial SR study23 also declines were recorded.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [22]
These three independent studies point out that restriction of sleep, either acutely or partially for a longer period, significantly affects serum lipid levels, as measured using mass spectrometry.
“these three independent studies point out that restriction of sleep, either acutely or partially for a longer period, significantly affects serum lipid levels, as measured using mass spectrometry.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [22]
In both studies, the majority of the altered, identified species consisted of lipid species (including phospholipids, sphingolipids, acylcarnitides and phosphatidylcholines).
“In both studies, the majority of the altered, identified species, consisted of lipid species (including phospholipids, sphingolipids, acylcarnitides and phosphatidylcholines).”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [22]
Two recent studies have measured lipid profiles in human blood samples using mass spectrometry analysis after short term total sleep restriction and partial sleep restriction for five days.
“Two recent studies have measured lipid profiles in human blood samples using mass spectrometry analysis after polar and non-polar extraction of the samples after a short term (24 h) total sleep restriction22 and a partial sleep restriction for five days23.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [22]
Total sleep deprivation causes a measurable perturbation of the human blood metabolome.
“Recent work indicates that total sleep deprivation induces a measurable perturbation to the blood metabolome (19)”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
Tryptophan is a major precursor for serotonin and melatonin and is elevated under acute total sleep deprivation.
“Trp is a major precursor for serotonin and melatonin and is elevated under acute total sleep deprivation (19).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
Twelve metabolites were common between this study and Davies et al., including PCs 32:1, 36:6, 38:4, 38:2, and 38:3; lysoPCs 14:0, 16:1, and 17:0; and acylcarnitines C5:0, C10:0, and C12:0.
“Twelve of these were common between the two studies, including PCs (32:1, 36:6, 38:4, 38:2, 38:3), lysoPCs (14:0, 16:1, 17:0), and acylcarnitines (C5:0, C10:0, C12:0).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
In both studies, tryptophan was elevated.
“In both studies, Trp was also elevated.”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
In the acute sleep deprivation study, all of the above-mentioned common metabolites were elevated.
“All of the above-mentioned metabolites were elevated in the acute sleep deprivation study.”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
Davies et al. identified metabolites that increased but found none that decreased under total sleep deprivation.
“The study of Davies et al. (19) identified metabolites that increased but found none that decreased under total sleep deprivation.”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
This study identified decreases in a number of metabolites as a function of sleep restriction, which were not part of the analytical platform used in Davies et al.
“Here we have identified decreases in a number metabolites as a function of SR, which were not part of the analytical platform used in the Davies et al. study (19).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [19]
Up to 20% of detectable metabolites in human matrices such as plasma and saliva exhibit daily rhythms.
“In addition to these mouse studies, human metabolome analyses also reveal that up to 20% of detectable metabolites in matrices such as plasma and saliva exhibit daily rhythms (44)(45)(46).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [46]
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Galanin Neurons Unite Sleep Homeostasis and α2-Adrenergic Sedation
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Self-citationCircadian Metabolism: From Mechanisms to Metabolomics and Medicine
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Bile acid metabolism and circadian rhythms
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Developing Biomarker Arrays Predicting Sleep and Circadian-Coupled Risks to Health
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Cerebral Metabolic Changes During Sleep
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Decoding aging clocks: New insights from metabolomics
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Melatonin: Countering Chaotic Time Cues
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- Authors
- Davies, S. K., Ang, J. E., Revell, V. L., Holmes, B., Mann, A., Robertson, F. P., Cui, N., Middleton, B., Ackermann, K., Kayser, M., Thumser, A. E., Raynaud, F. I., & Skene, D. J.
- Affiliations
- University of Surrey (GB)
- Institute of Cancer Research (GB)
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom;
- Erasmus MC (NL)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-07-07
- Volume
- 111
- Issue
- 29
- Pages
- 10761-10766
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4115565
- OpenAlex
- W2027141772
- Cited by
- 527
- References
- 52
- Citations by year
- 2026: 22 · 2025: 52 · 2024: 47 · 2023: 57 · 2022: 39 · 2021: 49 · 2020: 39 · 2019: 54 · 2018: 51 · 2017: 42 · 2016: 36 · 2015: 37 · 2014: 1
- FWCI
- 19.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- Cancer Research UK (11566)
- Biotechnology and Biological Sciences Research Council (BB/I019405/1)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- sleep deprivation, plasma metabolites, circadian rhythm, sleep-wake cycle, metabolomics, tryptophan, serotonin, taurine, acylcarnitines, glycerophospholipids, sphingolipids
- MeSH terms
- Humans, Male, Sleep Deprivation, Multivariate Analysis, Principal Component Analysis, Metabolomics, Metabolome
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