Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans

急性睡眠不足会导致人类全基因组 DNA 甲基化状态和代谢燃料利用发生组织特异性改变

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作者:Jonathan Cedernaes, Milena Schönke, Jakub Orzechowski Westholm, Jia Mi, Alexander Chibalin, Sarah Voisin, Megan Osler, Heike Vogel, Katarina Hörnaeus, Suzanne L Dickson, Sara Bergström Lind, Jonas Bergquist, Helgi B Schiöth, Juleen R Zierath, Christian Benedict

Abstract

Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.

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