Invited Review

Pflügers Archiv - European Journal of Physiology

, Volume 463, Issue 1, pp 15-22

First online:

A metabolic–transcriptional network links sleep and cellular energetics in the brain

  • Jonathan P. WisorAffiliated withWWAMI Medical Education Program and Department Of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University Email author 

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This review proposes a mechanistic link between cellular metabolic status, transcriptional regulatory changes and sleep. Sleep loss is associated with changes in cellular metabolic status in the brain. Metabolic sensors responsive to cellular metabolic status regulate the circadian clock transcriptional network. Modifications of the transcriptional activity of circadian clock genes affect sleep/wake state changes. Changes in sleep state reverse sleep loss-induced changes in cellular metabolic status. It is thus proposed that the regulation of circadian clock genes by cellular metabolic sensors is a critical intermediate step in the link between cellular metabolic status and sleep. Studies of this regulatory relationship may offer insights into the function of sleep at the cellular level.


Nicotinamide adenine dinucleotide Adenosine triphosphate Slow wave activity Sleep Circadian Adenosine monophosphate-activated protein kinase Glycogen Sirtuin Poly(ADP)ribosyl polymerase Peroxisome proliferator-activated receptor