Nav: Home

Curbing your enthusiasm for overeating

June 11, 2019

RIVERSIDE, Calif. -- Signals between our gut and brain control how and when we eat food. But how the molecular mechanisms involved in this signaling are affected when we eat a high-energy diet and how they contribute to obesity are not well understood.

Using a mouse model, a research team led by a biomedical scientist at the University of California, Riverside, has found that overactive endocannabinoid signaling in the gut drives overeating in diet-induced obesity by blocking gut-brain satiation signaling.

Endocannabinoids are cannabis-like molecules made naturally by the body to regulate several processes: immune, behavioral, and neuronal. As with cannabis, endocannabinoids can enhance feeding behavior.

The researchers detected high activity of endocannabinoids at cannabinoid CB1 receptors in the gut of mice that were fed a high-fat and sugar -- or Western -- diet for 60 days. This overactivity, they found, prevented the food-induced secretion of the satiation peptide cholecystokinin, a short chain of amino acids whose function is to inhibit eating. This resulted in the mice overeating. Cannabinoid CB1 receptors and cholecystokinin are present in all mammals, including humans.

Study results appear in 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," said Nicholas V. DiPatrizio, an assistant professor of biomedical sciences in the UCR School of Medicine who led the research team.

DiPatrizio explained that previous research by his group on a rat model showed that oral exposure to dietary fats stimulates production of the body's endocannabinoids in the gut, which is critical for the further intake of high-fat foods. Other researchers, he said, have found that levels of endocannabinoids in humans increased in blood just prior to and after eating a palatable high-energy food, and are elevated in obese humans.

"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," said Donovan A. Argueta, a doctoral student in DiPatrizio's lab and the first author of the research paper.

Previous attempts at targeting the cannabinoid CB1 receptors with drugs such as Rimonabant -- a CB1 receptor blocker -- failed due to psychiatric side effects. However, the DiPatrizio lab's current study suggests it is possible to target only the cannabinoid receptors in the gut for therapeutic benefits in obesity, greatly reducing the negative side effects.

The research team plans to work on getting a deeper understanding of how CB1 receptor activity 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 said. "We also plan to study how endocannabinoids control the release of other molecules in the intestine that influence metabolism."
-end-
Grants to DiPatrizio from the National Institute of Diabetes and Digestive and Kidney Diseases; and National Institute on Drug Abuse of the National Institutes of Health funded the study. Argueta, who graduates this summer, was supported by a Ford Foundation Dissertation Fellowship. They were joined in the study by UCR's Pedro A. Perez and Alexandros Makriyannis of the Center for Drug Discovery at Northeastern University, Boston.

The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 24,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of almost $2 billion. To learn more, email news@ucr.edu.

University of California - Riverside

Related Obesity Articles:

Should obesity be recognized as a disease?
With obesity now affecting almost a third (29%) of the population in England, and expected to rise to 35% by 2030, should we now recognize it as a disease?
Is obesity associated with risk of pediatric MS?
A single-center study of 453 children in Germany with multiple sclerosis (MS) investigated the association of obesity with pediatric MS risk and with the response of first-line therapy in children with MS.
Women with obesity prior to conception are more likely to have children with obesity
A systematic review and meta-analysis identified significantly increased odds of child obesity when mothers have obesity before conception, according to a study published June 11, 2019 in the open-access journal PLOS Medicine by Nicola Heslehurst of Newcastle University in the UK, and colleagues.
Obesity medicine association announces major updates to its adult obesity algorithm
The Obesity Medicine Association (OMA) announced the immediate availability of the 2019 OMA Adult Obesity Algorithm, with new information for clinicians including the relationship between Obesity and Cardiovascular Disease, Diabetes Mellitus, Dyslipidemia, and Cancer; information on investigational Anti-Obesity Pharmacotherapy; treatments for Lipodystrophy; and Pharmacokinetics and Obesity.
Systematic review shows risk of a child developing overweight or obesity is more than trebled by maternal obesity prior to pregnancy
New research presented at this year's European Congress on Obesity (ECO) in Glasgow, Scotland (April 28- May 1) reveals that the risk of a child becoming overweight or obese is more than trebled by maternal obesity prior to getting pregnant.
Eating later in the day may be associated with obesity
Eating later in the day may contribute to weight gain, according to a new study to be presented Saturday at ENDO 2019, the Endocrine Society's annual meeting in New Orleans, La.
How obesity affects vitamin D metabolism
A new Journal of Bone and Mineral Research study confirms that vitamin D supplementation is less effective in the presence of obesity, and it uncovers a biological mechanism to explain this observation.
Wired for obesity
In a multi-center collaboration, scientists at Children's Hospital Los Angeles and University of Cambridge discover a set of genes that help to establish brain connections governing body weight.
Sarcopenic obesity: The ignored phenotype
A new condition, that occurs in the presence of both sarcopenia and obesity and termed as ''sarcopenic obesity'', and that describes under the same phenotype the increase in body fat mass deposition, and the reduction in lean mass and muscle strength.
Study finds people with type 2 diabetes at higher risk of death from both obesity-related and non-obesity related cancers
Being overweight or obese may put adults with diabetes at greater risk of dying from cancer than their diabetes-free counterparts, particularly for obesity-related cancers such as those arising from the bowel, kidney, and pancreas in men and women, and from the breast and endometrium (lining of the uterus) in women.
More Obesity News and Obesity Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.