Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men
Abstract
Context: Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. Objective: This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. Intervention: In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230–0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. Main Outcome Measures: In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (−18%; P = .033) and CRY1 (−22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Conclusions: Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.
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One night of sleep deprivation leads to a reduction in glucose tolerance.
“One night of sleep deprivation (commonly experienced by 20% of the world's population who perform shift-work) leads to a reduction in glucose tolerance and concomitant alterations in the expression of skeletal muscle clock genes (i.e., Bmal1 and Cry1 gene expression [7]) and the content of clock proteins (i.e., BMAL1) [8]”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [7]
The detrimental effect of sleep loss on glucose metabolism may also be associated with misalignment of circadian rhythms.
“The detrimental effect of sleep loss on glucose metabolism may also be associated with the misalignment of circadian rhythms [7,8].”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [7]
One night of sleep deprivation leads to concomitant alterations in expression of skeletal muscle clock genes (Bmal1 and Cry1) and content of clock proteins (BMAL1).
“One night of sleep deprivation (commonly experienced by 20% of the world's population who perform shift-work) leads to a reduction in glucose tolerance and concomitant alterations in the expression of skeletal muscle clock genes (i.e., Bmal1 and Cry1 gene expression [7]) and the content of clock proteins (i.e., BMAL1) [8]”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [7]
Molecular markers of circadian rhythm are altered by a night of sleep deprivation.
“As many of the molecular processes that regulate mitochondrial content, function, and dynamics are regulated in a circadian manner [60,61] and considering that molecular markers of circadian rhythm are altered by a night of sleep deprivation [7,8], we also examined aspects of diurnal rhythmicity using the measures of peripheral skin temperature (obtained over 48 h, pre- and post-intervention) and”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [7]
Cedernaes et al. reported a decrease in Bmal1 mRNA expression in 15 participants following 24 h of sleep deprivation.
“This is in contrast to previous findings from Cedernaes et al. [7,8] who reported a decrease in Bmal1 mRNA expression in 15 participants following 24 h of sleep deprivation.”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [7]
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- Authors
- Cedernaes, J., Osler, M. E., Voisin, S., Broman, J.-E., Vogel, H., Dickson, S. L., Zierath, J. R., Schiöth, H. B., & Benedict, C.
- Affiliations
- Uppsala University (SE)
- Karolinska Institutet (SE)
- German Institute of Human Nutrition (DE)
- University of Gothenburg (SE)
- Corresponding author
- Cedernaes, Jonathan
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-09-01
- Volume
- 100
- Issue
- 9
- Pages
- E1255-E1261
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1815920130
- Cited by
- 188
- References
- 14
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 14 · 2023: 8 · 2022: 15 · 2021: 19 · 2020: 20 · 2019: 19 · 2018: 18 · 2017: 16 · 2016: 18 · 2015: 1 · 2014: 1
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- Brain Research Foundation
- AFA Försäkring
- Novo Nordisk
- Vetenskapsrådet
- Magnus Bergvalls Stiftelse
- Uppsala Universitet
- Svenska Läkaresällskapet
- Science for Life Laboratory
- Novo Nordisk Fonden (NNF13OC0004819, NNF14OC0009349, NNF14OC0011493, NNF12OC1016479)
- 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 › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- clock genes, DNA methylation, gene expression, shift work, skeletal muscle, subcutaneous adipose tissue, CRY1, Per1, Bmal1, serum cortisol, postprandial blood glucose, metabolic health
- MeSH terms
- Blood Glucose, Circadian Rhythm, Humans, Hydrocortisone, Male, Sleep, Sleep Deprivation, Gene Expression, Muscle, Skeletal, Cross-Over Studies, Epigenesis, Genetic, Young Adult, CLOCK Proteins, ARNTL Transcription Factors, Cryptochromes, Period Circadian Proteins, Circadian Clocks
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