Sleep deprivation is on a long list of risk factors for obesity, but how, exactly, does insufficient sleep fuel weight gain? A new study published in SLEEP suggests the answer lies within the endocannabinoid (eCB) system.

The eCB system is involved in the control of feeding, appetite, and energy homeostasis, the study authors reported — it’s also the system that plays a role in runner’s high. The eCB system is made up of cannabinoid CB1 and CB2 receptors, which naturally produce the compound that binds and activates these receptors, 2-arachidonoylglycerol (2-AG). Since short sleep in particular has been shown to increase obesity risk, as well as modestly increase energy need, the study authors hypothesized sleep deprivation activates 2-AG, which results in "appetite-enhancing effects."

"There are remarkable parallels between the effects of activation of the eCB system and the effect of experimental sleep restriction," they wrote. "Just as in a state of sleep debt, CB1 receptor activity increases feeding behavior in excess of energy need, reduces glucose tolerance, tends to reduce leptin levels and to promote ghrelin release, and stimulates reward and addiction."

For the study, the authors' recruited 14 healthy, non-obese volunteers aged 18 to 36 with a body mass index less than 28 (for men) and 27 (for women). Participants self-reported habitual sleep duration of 7.5 to 8.5 hours between 11 p.m. and 9 a.m., and all underwent overnight laboratory tests to rule out any existing sleep disorders. Glucose tolerance and fasting blood samples were also collected in the lab.

Participants then took part in two sleep experiments at the lab, with four weeks separating each experiment. In the first, participants spent four consecutive days sleeping 8.5 hours in bed each night, whereas in the second, participants spent four days sleeping 4.5 hours every night. And during waking hours, participants were limited to sedentary activities (except for napping), housed in a private room, and were only allowed dim lighting from the time they woke up until 10:30 p.m.

As for caloric intake, study participants were given identical meals three times a day, at 9 a.m., 2 p.m., and 7 p.m., after which researchers measured blood levels of the satiety hormone leptin, appetite hormone ghrelin, and endocannabinoids.

The results showed that after 8.5 hours of sleep, participants woke up with low levels of 2-AG, though they peaked after lunchtime and decreased as the day went on. But after the study authors restricted participant's sleep to 4.5 hours, 2-AG levels increased by 33 percent, peaking at 2 p.m. and staying elevated until about 9 p.m.

When sleep deprived, participants reported increases in hunger and appetite around the same time their 2-AG levels spiked, perhaps explained by the lower levels of leptin and higher levels of ghrelin. Not only that, but they were more likely to choose snacks with 50 percent more calories and twice the fat than the snacks well-rested participants chose.

Sleep-deprived people had a harder time resisting "palatable snacks," strengthening the idea sleep deprivation contributes to weight gain.

"This study supports the novel insight that sleep restriction may not only lead to increased caloric intake due to changes in homeostatic regulation of energy balance, as has been shown by this group and others, but also by changes in...aspects of food consumption," Dr. Frank Scheer, of Harvard University's Brigham and Women's Hospital, said in a statement.

The question remains, however, whether an environmental, behavioral, or pharmacological intervention would work best to "decrease the signaling through the endocannabinoid system to specifically target the reward value of food and prevent overeating following inadequate sleep," Scheer said — or just in general.

Regardless, the study authors believe their findings affirm the idea insufficient sleep may contribute to the risk and prevalence of obesity. They agree, however, more research needs to be done in order to gain an "increased understanding of the mechanisms linking insufficient sleep and the risk of weight gain is important to design preventive strategies."

Source: Hanlon EC, Tasali E, Leproult R, Stuhr KL, Doncheck E, de Wit H, Hillard CJ, Van Cauter E. Sleep restriction enhances the daily rhythm of circulating levels of endocannabinoid 2-arachidonoylglycerol. SLEEP. 2016.