Sleep loss induces tissuespecific epigenetic a. transcriptional alterations to circadian clock genes
Shift workers are at increased risk of metabolic morbidities.
Clock genes are known to regulate metabolic processes in peripheral tissues, e.g. glucose oxidation.
Objective: 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, 2-period, 2-condition, crossover clinical study, fifteen healthy men underwent two experimental sessions: one-night sleep (2230–0700h) 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-hr-post oral glucose load plasma glucose concentrations were determined.
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.
- 1Department of Neuroscience, Uppsala University, Husargatan 3, Box
- 593, 751 24 Uppsala, Sweden
- 2Department of Molecular Medicine and Surgery, Karolinska Institutet,
- 171 77 Stockholm, Sweden
- 3Department of Experimental Diabetology, German Institute of Human
- Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
4Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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