title: Sleep Restriction Enhances the Daily Rhythm of Circulating Levels of Endocannabinoid 2-Arachidonoylglycerol.
abstract: OBJECTIVE
  Increasing evidence from laboratory and epidemiologic studies indicates that insufficient sleep may be a risk factor for obesity. Sleep curtailment results in stimulation of hunger and food intake that exceeds the energy cost of extended wakefulness, suggesting the involvement of reward mechanisms. The current study tested the hypothesis that sleep restriction is associated with activation of the endocannabinoid (eCB) system, a key component of hedonic pathways involved in modulating appetite and food intake.
  
  
  METHODS
  In a randomized crossover study comparing 4 nights of normal (8.5 h) versus restricted sleep (4.5 h) in healthy young adults, we examined the 24-h profiles of circulating concentrations of the endocannabinoid 2-arachidonoylglycerol (2-AG) and its structural analog 2-oleoylglycerol (2-OG). We concomitantly assessed hunger, appetite, and food intake under controlled conditions.
  
  
  RESULTS
  A robust daily variation of 2-AG concentrations with a nadir around the middle of the sleep/overnight fast, followed by a continuous increase culminating in the early afternoon, was evident under both sleep conditions but sleep restriction resulted in an amplification of this rhythm with delayed and extended maximum values. Concentrations of 2-OG followed a similar pattern, but with a lesser amplitude. When sleep deprived, participants reported increases in hunger and appetite concomitant with the afternoon elevation of 2-AG concentrations, and were less able to inhibit intake of palatable snacks.
  
  
  CONCLUSIONS
  Our findings suggest that activation of the eCB system may be involved in excessive food intake in a state of sleep debt and contribute to the increased risk of obesity associated with insufficient sleep.
  
  
  CONCLUSIONS
  A commentary on this article appears in this issue on page 495.
authors.affiliation: University of Chicago Sleep, Health and Metabolism Center (SMAHC), Department of Medicine, Chicago, IL.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Hanlon
authors.affiliation: University of Chicago Sleep, Health and Metabolism Center (SMAHC), Department of Medicine, Chicago, IL.
authors.forename: Esra
authors.initials: E
authors.lastname: Tasali
authors.affiliation: Université Libre de Bruxelles, Neuropsychology and Functional Neuroimaging Research Group (UR2NF) at the Center for Research in Cognition and Neurosciences (CRCN) and the ULB Neuroscience Institute (UNI) Campus du Solbosch, Brussels, Belgium.
authors.forename: Rachel
authors.initials: R
authors.lastname: Leproult
authors.affiliation: Medical College of Wisconsin, Neuroscience Research Center, Department of Pharmacology and Toxicology, Milwaukee, WI.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Stuhr
authors.affiliation: Medical College of Wisconsin, Neuroscience Research Center, Department of Pharmacology and Toxicology, Milwaukee, WI.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Doncheck
authors.affiliation: University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL.
authors.forename: Harriet
authors.initials: H
authors.lastname: de Wit
authors.affiliation: Medical College of Wisconsin, Neuroscience Research Center, Department of Pharmacology and Toxicology, Milwaukee, WI.
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.affiliation: University of Chicago Sleep, Health and Metabolism Center (SMAHC), Department of Medicine, Chicago, IL.
authors.forename: Eve
authors.initials: E
authors.lastname: Van Cauter
mesh_terms: D000293:Adolescent; D000328:Adult; D001069:Appetite Regulation / Q000502:physiology; D001095:Arachidonic Acids / Q000097:blood*; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D004435:Eating / Q000502:physiology; D063388:Endocannabinoids / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D005989:Glycerides / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D006815:Hunger / Q000502:physiology; D006963:Hyperphagia / Q000097:blood* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000097:blood / Q000209:etiology; D012201:Reward; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D014851:Wakefulness; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate; C505247:2-oleoylglycerol
keywords: appetite; endocannabinoid; hedonic food intake; hunger; obesity; sleep restriction