Curb your enthusiasm for overeating

Signals between our intestines and our brain control how and when we eat food. But we do not fully understand the molecular mechanisms involved in this signaling when we eat a diet rich in energy and how they contribute to obesity.

Using a mouse model, a research team led by a biomedical scientist at the University of California, Riverside, discovered that overactive endocannabinoid signaling in the gut led to overeating in diet-induced obesity by blocking the signaling of satiety between the brain and the intestines.

Endocannabinoids are molecules similar to cannabis naturally manufactured by the body to regulate several processes: immune, behavioral and neuronal. As with cannabis, endocannabinoids can improve eating behavior.

The researchers detected a high activity of BC endocannabinoids₁ Receptors in the intestine of mice fed a diet high in fat and sugar – or western – for 60 days. They discovered that this overactivity prevented the food-induced secretion of satiety peptide, cholecystokinin, a short chain of amino acids whose role is to inhibit the diet. This led the mice to overeat. Cannabinoid CB₁ Receptors and cholecystokinin are present in all mammals, including humans.

The results of the study appear in the newspaper Frontiers in physiology, an open access journal.

"If drugs could be developed to target these cannabinoid receptors so as not to inhibit the release of satiety peptides during excessive diets, we would be well on our way to combating the prevalence of "Obesity affects millions of people in the country and around the world," said Nicholas V. DiPatrizio, an assistant professor of biomedical sciences at the UCR School of Medicine, who led the research team.

DiPatrizio explained that previous research conducted by his group on a rat model had shown that oral exposure to dietary fats stimulated the production of bodily endocannabinoids in the intestine, which was essential for the subsequent consumption of high fat foods. Other researchers, he said, discovered that endocannabinoid levels in humans increased in the blood just before and after consuming a tasty and highly energetic food. , and were raised in the obese man.

"Studies in humans have shown that diet-related nutrition leads to an increase in endocannabinoids, but it remains to be determined whether endocannabinoids control the release of satiety peptides," said Donovan A. Argueta, a PhD student from DiPatrizio's laboratory and the first author of the research paper.

Previous attempts to target the CB cannabinoid₁ receptors with drugs such as Rimonabant, a CB₁ receptor blocker – failure due to psychiatric side effects. However, the current study of the DiPatrizio laboratory suggests that it is possible to target only the cannabinoid receptors of the intestine to obtain therapeutic benefits in the treatment of obesity, thus reducing significantly adverse effects.

The research team plans to better understand how CB works₁ Receptor activity is related to cholecystokinin.

"We would also like to better understand how specific components of the Western diet – fats and sucrose – lead to deregulation of the endocannabinoid system and intestinal signaling," DiPatrizio said. "We also plan to study how endocannabinoids control the release of other molecules in the gut that affect metabolism."