Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, Illinois.
Department of Pharmacology and Toxicology, Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin.
J Clin Endocrinol Metab. 2020 Mar 1;105(3):792-802. doi: 10.1210/clinem/dgaa028.
The endocannabinoid (eCB) system partly controls hedonic eating, a major cause of obesity. While some studies suggested an overactivation of the eCB system in obesity, peripheral levels of eCBs across the 24-hour cycle have not been characterized in obese individuals despite the fact that in lean adults, levels of the eCB 2-arachidonoylglycerol (2-AG) vary across the day.
We sought to examine 24-hour profiles of serum concentrations of 2-AG in healthy obese and nonobese adults, under well-controlled laboratory conditions. We also simultaneously assessed 24-hour profiles of 2-oleoylglycerol (2-OG), leptin, and cortisol in each participant.
With fixed light-dark and sleep-wake cycles, blood sampling was performed over an entire 24-hour period, including identical meals at 0900, 1400, and 1900.
Twelve obese (8 women, mean body mass index [BMI]: 39.1 kg/m2) and 15 nonobese (6 women; mean BMI: 23.6 kg/m2) healthy adults were studied.
We observed a 24-hour variation of 2-AG levels in obese individuals but, relative to nonobese adults, the amplitude was dampened and the timings of the nadir and peak were delayed by 4 to 5 hours. The profile of 2-OG was similarly misaligned. In contrast, when expressed relative to the 24-hour mean level, the 24-hour rhythm of cortisol and leptin were similar in obese and nonobese participants.
Obesity appears to be associated with a dampening and delay of the 24-hour variation of eCB activity relative to the central circadian signal as well as to the daily leptin rhythm. This misalignment may play a role in the pathophysiology of obesity.
内源性大麻素（eCB）系统部分控制愉悦性进食，这是肥胖的主要原因之一。虽然一些研究表明肥胖症患者的 eCB 系统过度活跃，但尽管在瘦成年人中，eCB 2-花生四烯酰甘油（2-AG）的水平在一天中会发生变化，但尚未描述肥胖个体在 24 小时周期内的外周 eCB 水平。
我们试图在严格控制的实验室条件下，检查健康肥胖和非肥胖成年人的血清 2-AG 浓度 24 小时谱。我们还同时评估了每个参与者的 24 小时 2-油酰甘油（2-OG）、瘦素和皮质醇的水平。
在固定的光-暗和睡眠-觉醒周期下，在整个 24 小时期间进行血液采样，包括在 0900、1400 和 1900 点进行相同的膳食。
研究了 12 名肥胖者（8 名女性，平均体重指数[BMI]：39.1kg/m2）和 15 名非肥胖者（6 名女性；平均 BMI：23.6kg/m2）。
我们观察到肥胖者 2-AG 水平存在 24 小时变化，但与非肥胖成年人相比，振幅减弱，最低点和最高点的时间延迟了 4 到 5 小时。2-OG 的水平也类似地错位。相比之下，当相对于 24 小时平均水平表示时，肥胖和非肥胖参与者的皮质醇和瘦素的 24 小时节律相似。
肥胖症似乎与 eCB 活性的 24 小时变化相对于中央生物钟信号以及每日瘦素节律的减弱和延迟有关。这种失准可能在肥胖的病理生理学中发挥作用。
