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Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt
Journal article   Open access   Peer reviewed

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

Aalim M Weljie, Peter Meerlo, Namni Goel, Arjun Sengupta, Matthew S Kayser, Ted Abel, Morris J Birnbaum, David F Dinges and Amita Sehgal
Proceedings of the National Academy of Sciences - PNAS, Vol.112(8), pp.2569-2574
02/24/2015
DOI: 10.1073/pnas.1417432112
PMCID: PMC4345602
PMID: 25675494
url
https://doi.org/10.1073/pnas.1417432112View
Published (Version of record) Open Access

Abstract

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. Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets ( n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction ( P < 0.05, false-discovery rate < 0.2). Elevated phospholipids were also noted after sleep restriction in both species, as well as metabolites associated with an oxidizing environment. In addition, polar metabolites reflective of neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.
 Biological Sciences Mass Spectrometry sleep deprivation metabolomics sleep restriction lipidomics

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