Curb your enthusiasm for overeating

RIVERSIDE, California – 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 gut of mice fed for 60 days with a diet rich in sugars or sugar. 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 are published in the journal 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 badistant 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.

"Research in humans has shown that consumption badociated with an appetizing diet 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 doctoral student of DiPatrizio. 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."

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Grants to DiPatrizio from the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Institutes of Health's National Drug Abuse Control Institute. Argueta, who is finishing her studies this summer, was supported by a Ford Foundation Fellowship. Pedro A. Perez of UCR and Alexandros Makriyannis of the Center for Drug Discovery at Northeastern University in Boston participated in the study.

The University of California, Riverside, is a doctoral research university, a living laboratory for a revolutionary exploration of critical issues for Southern California, the state, and communities around the world. Reflecting California's diverse culture, UCR has more than 24,000 students. The campus opened a medical school in 2013 and reached the heart of the Coachella Valley through the UCR Palm Desert Center. The campus has an annual economic impact of nearly $ 2 billion on the statewide. For more information, send an email to [email protected].

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