title: Circadian rhythm of circulating levels of the endocannabinoid 2-arachidonoylglycerol.
abstract: BACKGROUND
  The endocannabinoid (eCB) system is involved in the regulation of food intake and of peripheral metabolism. Although the cross talk between energy metabolism and the circadian system is well documented, little is known about a potential circadian modulation of human eCB activity.
  
  
  OBJECTIVE
  The objective of the study was to define the 24-hour profile of circulating levels of the most abundant endogenous ligand of the CB1 receptor, 2-arachidonoylglycerol (2-AG), in healthy young nonobese adults studied under controlled bedtime, dietary, and activity conditions.
  
  
  METHODS
  Fourteen subjects participated in this 4-day laboratory study with fixed light-dark cycles, standardized meals, and bedtimes. Sleep was recorded each night. On the third day, blood sampling at 15- to 30-minute intervals began at 9:30 pm and continued for 24 hours. Cortisol, leptin, and ghrelin were assayed on all samples, whereas the levels of 2-AG and its structural analog, 2-oleoylglycerol (2-OG), were measured at 60-minute intervals.
  
  
  RESULTS
  All participants exhibited a large circadian variation of 2-AG serum concentrations with a nadir around midsleep, coincident with the middle of the overnight fast. Levels of 2-AG increased continually across the morning, peaking in the early to midafternoon. Peak values represented, on average, a nearly 3-fold increase above nocturnal nadir levels. Concentrations of 2-OG followed a similar pattern, although with a shorter morning increase and lower amplitude.
  
  
  CONCLUSIONS
  The findings demonstrate that activity of the eCB system is profoundly modulated by circadian rhythmicity and suggest that its impact on the regulation of food intake is suppressed during sleep and is maximal during early to midafternoon.
authors.affiliation: Sleep, Metabolism, and Health Center (E.C.H., E.T., E.V.C.), Department of Medicine, and Department of Psychiatry and Behavioral Neuroscience (H.d.W.), University of Chicago, Chicago, Illinois 60637; Neuropsychology and Functional Neuroimaging Research Group (R.L.), Center for Research in Cognition and Neurosciences and the Université Libre de Bruxelles Neuroscience Institute, Université Libre de Bruxelles, B-1050 Bruxelles, Brussels, Belgium; and Neuroscience Research Center (K.L.S., E.D., C.J.H.), Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
authors.forename: E C
authors.initials: EC
authors.lastname: Hanlon
authors.forename: E
authors.initials: E
authors.lastname: Tasali
authors.forename: R
authors.initials: R
authors.lastname: Leproult
authors.forename: K L
authors.initials: KL
authors.lastname: Stuhr
authors.forename: E
authors.initials: E
authors.lastname: Doncheck
authors.forename: H
authors.initials: H
authors.lastname: de Wit
authors.forename: C J
authors.initials: CJ
authors.lastname: Hillard
authors.forename: E
authors.initials: E
authors.lastname: Van Cauter
mesh_terms: D000293:Adolescent; D000328:Adult; D001095:Arachidonic Acids / Q000097:blood*; D002940:Circadian Rhythm / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D054439:Ghrelin / Q000097:blood; D005989:Glycerides / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D012890:Sleep / Q000502:physiology*; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D054439:Ghrelin; D005989:Glycerides; D020738:Leptin; C094503:glyceryl 2-arachidonate; D006854:Hydrocortisone