Hanlon E C, Tasali E, Leproult R, Stuhr K L, Doncheck E, de Wit H, Hillard C J, Van Cauter E
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.
J Clin Endocrinol Metab. 2015 Jan;100(1):220-6. doi: 10.1210/jc.2014-3455.
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.
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.
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.
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.
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.
内源性大麻素（eCB）系统参与食物摄入和外周代谢的调节。尽管能量代谢与昼夜节律系统之间的相互作用已有充分记录，但关于人类eCB活性的潜在昼夜调节知之甚少。
本研究的目的是在受控的就寝时间、饮食和活动条件下，确定健康年轻非肥胖成年人中CB1受体最丰富的内源性配体2-花生四烯酸甘油酯（2-AG）循环水平的24小时变化情况。
14名受试者参与了这项为期4天的实验室研究，研究采用固定的明暗周期、标准化饮食和就寝时间。每晚记录睡眠情况。在第三天，从晚上9:30开始每隔15至30分钟采集一次血样，并持续24小时。对所有样本进行皮质醇、瘦素和胃饥饿素检测，而2-AG及其结构类似物2-油酰甘油（2-OG）的水平每隔60分钟测量一次。
所有参与者的2-AG血清浓度均呈现出较大的昼夜变化，在睡眠中期左右达到最低点，这与夜间禁食的中间时段一致。2-AG水平在整个上午持续升高，在下午早些时候至中午达到峰值。峰值平均比夜间最低点水平高出近3倍。2-OG的浓度遵循类似模式，尽管上午升高时间较短且幅度较小。
研究结果表明，eCB系统的活性受到昼夜节律的深刻调节，提示其对食物摄入调节的影响在睡眠期间受到抑制，而在下午早些时候至中午达到最大。
