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Curbing your enthusiasm for overeating

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From L to R: Nicholas DiPatrizio, Pedro Perez, and Donovan Argueta. Credit: UCR/Stan Lim.

Signals between our intestine and mind management how and once we eat food. But how the molecular mechanisms concerned on this signaling are affected once we eat a high-energy weight loss program and the way they contribute to weight problems will not be nicely understood.

Using a mouse mannequin, a analysis crew led by a biomedical scientist on the University of California, Riverside, has discovered that overactive endocannabinoid signaling within the intestine drives overeating in diet-induced weight problems by blocking gut-brain satiation signaling.

Endocannabinoids are cannabis-like molecules made naturally by the physique to control a number of processes: immune, behavioral, and neuronal. As with hashish, endocannabinoids can improve feeding habits.

The researchers detected excessive exercise of endocannabinoids at cannabinoid CB1 receptors within the intestine of mice that have been fed a high-fat and sugar—or Western—weight loss program for 60 days. This overactivity, they discovered, prevented the food-induced secretion of the satiation peptide cholecystokinin, a brief chain of amino acids whose operate is to inhibit eating. This resulted within the mice overeating. Cannabinoid CB1 receptors and cholecystokinin are present in all mammals, together with people.

Study outcomes seem within the journal Frontiers in Physiology, an open-access journal.

“If drugs could be developed to target these cannabinoid receptors so that the release of satiation peptides is not inhibited during excessive eating, we would be a step closer to addressing the prevalence of obesity that affects millions of people in the country and around the world,” mentioned Nicholas V. DiPatrizio, an assistant professor of biomedical sciences within the UCR School of Medicine who led the analysis crew.

DiPatrizio defined that earlier analysis by his group on a rat mannequin confirmed that oral publicity to dietary fat stimulates manufacturing of the physique’s endocannabinoids within the intestine, which is essential for the additional consumption of high-fat meals. Other researchers, he mentioned, have discovered that ranges of endocannabinoids in people elevated in blood simply previous to and after eating a palatable high-energy food, and are elevated in overweight people.

“Research in humans has shown that eating associated with a palatable diet led to an increase in endocannabinoids—but whether or not endocannabinoids control the release of satiation peptides is yet to be determined,” mentioned Donovan A. Argueta, a doctoral pupil in DiPatrizio’s lab and the primary writer of the analysis paper.

Previous makes an attempt at focusing on the cannabinoid CB1receptors with medicine comparable to Rimonabant—a CB1 receptor blocker—failed attributable to psychiatric unwanted effects. However, the DiPatrizio lab’s present research suggests it’s potential to focus on solely the cannabinoid receptors within the intestine for therapeutic advantages in weight problems, tremendously decreasing the unfavorable unwanted effects.

The analysis crew plans to work on getting a deeper understanding of how CB1 receptor exercise is linked to cholecystokinin.

“We would also like to get a better understanding of how specific components of the Western diet—fat and sucrose—lead to the dysregulation of the endocannabinoid system and gut-brain signaling,” DiPatrizio mentioned. “We also plan to study how endocannabinoids control the release of other molecules in the intestine that influence metabolism.”


Study explains how western weight loss program results in overeating and weight problems


More data:
Donovan A. Argueta et al, Cannabinoid CB1 Receptors Inhibit Gut-Brain Satiation Signaling in Diet-Induced Obesity, Frontiers in Physiology (2019). DOI: 10.3389/fphys.2019.00704

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University of California – Riverside

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Curbing your enthusiasm for overeating (2019, June 11)
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