Cited by 164Circadian rhythm and melatoninSleep and Wakefulness ResearchSleep and Work-Related Fatigue

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index; 4 of the 51 sources its claims cite were checked for support.

Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt

Open access

Abstract

Significance: Reduced sleep duration is a hallmark of modern-day society and is increasingly associated with medical conditions, such as diabetes, obesity, metabolic syndrome, and cardiovascular disease. Here we present data from a rat model and human clinical study of chronic sleep restriction, both revealing that two metabolites in blood, oxalic acid and diacylglycerol 36:3, are quantitatively depleted under sleep-restricted conditions and restored after recovery sleep. Our findings also reveal a significant overall shift in lipid metabolism, with higher levels of phospholipids in both species and evidence of a systemic oxidative environment. This work provides a potential link between the known pathologies of reduced sleep duration and metabolic dysfunction.

Overview

Integrity signals

Registry

Crossref · 10.1073/pnas.1417432112

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

45 Own result · 39 Not checked yet · 29 Own interpretation · 10 Own method · 3 Partly supported · 1 Supported · accuracy not yet measured

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  • Probably not a substantial claim. 32
  • It may state two separate claims as one. 36
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  • The paper relies on this without support.

    Tryptophan is a precursor for liver synthesis of nicotinic acid, which interconverts with nicotinamide.

    “Trp is also the precursor to liver synthesis of nicotinic acid (vitamin B3), which interconverts with the amide form, nicotinamide.”
  • The paper relies on this without support.

    Phenylalanine is a precursor to dopamine, norepinephrine, and epinephrine via tyrosine.

    “Phe is also a precursor to several neurotransmitters, including dopamine, norepinephrine, and epinephrine via tyrosine.”
  • The paper relies on this without support.

    Pipecolic acid is a lysine metabolite unique to gut microflora.

    “pipecolic acid is a metabolite of lysine unique to gut microflora”
  • The paper relies on this without support.

    Endogenous substrates for oxalate synthesis include glycolate in peroxisomes and hydroxyproline.

    “Endogenous substrates for oxalate synthesis include glycolate in peroxisomes and hydroxyproline.”
  • The paper relies on this without support.

    The rat and human sleep restriction protocols produce comparable sleep debt for cross-species marker comparison.

    “we compared the list of significantly altered metabolites in rats and humans (Fig. 4).”
  • The paper relies on this without support.

    Activity may account for much of the effect of wakefulness itself.

    “In our rat study, the effects of activity-which may account for much of the effect of wake per se-were controlled by including a FA group.”
  • The paper relies on this without support.

    A 10- to 12-hour fast before sampling allows observed metabolic changes to be attributed to sleep or sleep restriction rather than other factors.

    “Thus, we also attempted to separate the metabolic effects from the sleep effects by enforcing a 10-to 12-h fasting period before metabolomic sampling, such that observed changes could be attributed to sleep/sleep restriction effects.”
  • The paper relies on this without support.

    Arachidonic acid is the substrate for COX-2.

    “Our results further indicate a significant clustering relationship between oxalate and arachidonic acid (Fig. S4), which is the substrate for COX-2, although we note that arachidonic acid was not significantly changed by our criteria.”
  • The paper relies on this without support.

    PPARs play a critical role in lipid and glucose metabolism.

    “One mechanism may be via the induction of PPARs, which play a critical role in lipid and glucose metabolism.”
  • The paper relies on this without support.

    Oleoylethanolamide is a potent activator of PPAR-α.

    “Oleoylethanolamide, a potent activator of PPAR-α, is also elevated in CSF, and to a lesser extent in serum of sleep-deprived humans (51).”
  • The paper relies on this without support.

    Glyoxylate is a common precursor to both oxalate and glycine in peroxisomes.

    “Reduction in both oxalate (humans and rats) and glycine (rats, SR5) might be explained by depletion of glyoxylate, which is a common precursor to both substances in peroxisomes.”
  • The paper relies on this without support.

    Peroxisomal β-oxidation preferentially processes longer-chain fatty acids.

    “Furthermore, the reduced levels of long-chain TGs and elevation in shorter-chain TGs observed in humans may reflect peroxisomal β-oxidation processes that are preferential for longer-chain fatty acids.”
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Metadata

Authors
Weljie, A. M., Meerlo, P., Goel, N., Sengupta, A., Kayser, M. S., Abel, T., Birnbaum, M. J., Dinges, D. F., & Sehgal, A.
Affiliations
  • Department of Pharmacology,
  • University of Groningen (NL)
  • Department of Psychiatry,
  • University of Pennsylvania (US)
  • Howard Hughes Medical Institute (US)
Venue
Proceedings of the National Academy of Sciences
Published
2015-02-09
Volume
112
Issue
8
Pages
2569-2574
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1981928051
Cited by
158
References
53
Citations by year
2026: 8 · 2025: 16 · 2024: 21 · 2023: 15 · 2022: 13 · 2021: 12 · 2020: 13 · 2019: 10 · 2018: 17 · 2017: 12 · 2016: 14 · 2015: 7
FWCI
9.24
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
  • Department of Navy, Office of Naval Research Award (N00014-11-1-0361)
  • National Aeronautics and Space Administration (NCC 9-58, NNX14AN49G)
  • HHS | NIH | National Institute of Nursing Research (R01 NR004281)
  • DOD | Defense Advanced Research Projects Agency (W911NF1010093)
  • Howard Hughes Medical Institute (-)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords
sleep restriction, sleep debt, oxalic acid, serum metabolomics, sleep deprivation, metabolic dysfunction, phospholipids, peroxisome proliferator-activated receptors, circadian clock, neurotransmitters, nicotinic acid, intestinal metabolism, oxidative stress, human-rat comparison
MeSH terms
Animals, Circadian Rhythm, Diglycerides, Disease Models, Animal, Energy Metabolism, Female, Humans, Male, Middle Aged, Niacinamide, Phenotype, Sleep Deprivation, Species Specificity, Time Factors, Reproducibility of Results, Biomarkers, Rats, Sprague-Dawley, Neurotransmitter Agents, Oxidative Stress, Oxalic Acid, Gastrointestinal Tract, PPAR gamma, Metabolomics, Metabolome, Young Adult, Microbiota

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