Findings from a study conducted by University of California scientists have identified the role the human endocannabinoid system plays in food consumption, energy balance and reward.
The system is located throughout the human body, including the brain and all peripheral organs.
By ensuring that endocannabinoids— lipid signalling molecules produced by the body—do not bind to endocannabinoid receptors, the team thinks this may form a basis to treat eating disorders including western diet-induced obesity.
The findings point towards targeting the peripheral receptors that bypass those located in the brain. The aim of the researchers was to avoid crossing the blood-brain barrier and interacting with central brain mechanisms.
Previous approaches that did cross this barrier and were effective in treating obesity and metabolic syndrome in humans were met with severe psychiatric side effects, including depression and even suicide.
Standard chow vs. western diet
Dr Nicholas DiPatrizio, an assistant professor of biomedical sciences at the University of California, who led the research project, began feeding eight-week old male mice a diet containing either standard lab rodent chow ((SD) 13.4% kcal as fat, 56% kcal from carbohydrates, mostly starch).
These mice were in contrast to mice fed a western-style diet ((WD) 40% kcal as fat, 43% kcal from carbohydrates, mostly sucrose). Both groups kept up the regimen for 60 days.
As expected, the WD mice rapidly gained body weight and became obese, and displayed hyperphagia—a condition characterised by a huge desire for food resulting in excessive food intake.
The team found that blocking the actions of the endocannabinoids with inhibitors of peripheral cannabinoid receptors normalised food consumption and meal habits in the WD-induced obese mice to similar levels found in the mice fed standard chow.
“This suggests that these elevations in peripheral endocannabinoid signalling are critical in driving hyperphagia associated with a western diet,” said study co-author Donovan Argueta, a bioengineering Ph.D. student.
Elevated levels of endocannabinoids in obese human subjects have previously been documented suggesting that this mechanism may be overactive in the onset of human obesity.
The study’s authors now hope to look at whether the mechanisms found in rodents apply to humans.
Previous research looking into subjects of normal and obese weight suggest that consumption of highly palatable foods was associated with elevated levels of the endocannabinoid 2-AG in the blood.
In comparison to subjects of a normal weight, levels of 2-AG in the blood were found to be raised in obese women, and both 2-AG and anandamide, another endocannabinoid, were elevated in the saliva of obese males and females.
The researchers added that it remained to be determined, however, if circulating endocannabinoids also directly interacted with feeding- and reward-related pathways in the brain.
Source: Physiology & Behavior
Published online ahead of print: doi.org/10.1016/j.physbeh.2016.12.044
“Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity.”
Authors: Donovan Arguetaa, Nicholas DiPatrizio et al.