OR09-1 Circadian rhythm of circulating endocannabinoid (EC), 2-arachidonoylglycerol (2-AG), concentrations following normal and restricted sleep

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR09-Obesity: Physiologic Responses to Energy Balance Disruption
Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 11:30 AM
Room 307 (Moscone Center)
Erin C Hanlon*1, Kara Stuhr2, Rachel Leproult1, Esra Tasali3, Harriet de Wit1, Cecilia J Hillard2 and Eve Van Cauter1
1University of Chicago, Chicago, IL, 2Medical College of Wisconsin, Milwaukee, WI, 3The University of Chicago, Chicago, IL
Evidence from laboratory and epidemiologic studies suggest that insufficient sleep duration may be a contributing factor to the epidemic of obesity. The EC system, a pharmacotherapeutic target for obesity treatment, mediates the hedonic control of feeding, and modulates reward mechanisms. Stimulation of the EC system could be involved in the risk in overeating associated with sleep loss. The roles of sleep and circadian rhythmicity in modulating circulating EC lipids are not known as previous studies have only assessed single time points or narrow time intervals. We examined the 24-h profile of (2-AG), and its structural analog 2-oleoylglycerol (2-OG), which does not bind cannabinoid receptors, in healthy subjects and determined the impact of recurrent partial sleep restriction.

In a randomized cross over design, nine healthy subjects (age:23 ± 1yrs; BMI:23.6±0.7kg/m2) were studied in the laboratory with controlled energy expenditure and caloric consumption.  Blood sampling was performed for 24-h following two nights of normal sleep (2300-0730) or partial sleep restriction (0100-0530).  Samples taken at 60min intervals were assayed with liquid chromatography electrospray ionization-mass spectrometry (LC-ES-MS), for detection of 2-AG and 2-OG.

Both 2-AG and 2-OG display clear circadian rhythms with a nadir around mid sleep and peak levels in the early afternoon. Following sleep restriction, the amplitude of the rhythm is significantly increased for both lipids (2-AG: 151 ±24 vs 126 ±24pmol/ml, p = 0.01; 2-OG 894±120 vs 709±85pmol/ml, p = 0.005), due to an increase in peak levels (2-AG: 386 ±60 vs 335 ±61 pmol/ml, p = 0.008; 2-OG: 3329±284 pmol/ml vs 3138 ±255 pmol/ml, p = 0.08). Mean 24-h levels of 2-AG and 2-OG were highly correlated during the normal sleep condition (r = 0.80, p < 0.05) and during the restriction condition (r = 0.84, p < 0.05). Moreover, despite the two conditions being separated by at least one month, mean 24-h levels were highly correlated between the normal and restricted sleep sessions for both 2-AG (r = 0.98,  p < 0.001) and 2-OG (r = 0.83, p = 0.005), indicating within-subject reproducibility.

This study provides the first demonstration of a robust circadian rhythm of human plasma EC levels and reveals that sleep restriction results in increased amplitude of the mid-sleep to early afternoon rise of both 2-AG and 2-OG.  Elevation of peak daytime levels of EC may contribute to the risk of overeating associated with sleep deprivation.

Nothing to Disclose: ECH, KS, RL, ET, HD, CJH, EV

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The University of Chicago Institute for Translational Medicine Pilot Projects in Translational and Clinical Studies (PPTCS) Award to HDW, CJH, and EVC.
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