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 from Brightsurf:

11 years of data add to the evidence for using testosterone therapy to treat obesity, including as an alternative to obesity surgery
New research covering 11 years of data presented at this year's European and International Congress on Obesity (ECOICO 2020) show that, in obese men suffering from hypogonadism (low testosterone), treatment with testosterone injections lowers their weight and improves a wide range of other metabolic parameters.

Overlap between immunology of COVID-19 and obesity could explain the increased risk of death in people living with obesity, and also older patients
Data presented in a special COVID-19 session at the European and International Congress on Obesity (ECOICO 2020) suggests that there are overlaps between the immunological disturbances found in both COVID-19 disease and patients with obesity, which could explain the increased disease severity and mortality risk faced by obese patients, and also elderly patients, who are infected by the SARS-CoV-2 virus that causes COVID-19 disease.

New obesity guideline: Address root causes as foundation of obesity management
besity management should focus on outcomes that patients consider to be important, not weight loss alone, and include a holistic approach that addresses the root causes of obesity, according to a new clinical practice guideline published in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.191707.

Changing the debate around obesity
The UK's National Health Service (NHS) needs to do more to address the ingrained stigma and discrimination faced by people with obesity, says a leading health psychologist.

Study links longer exposure to obesity and earlier development of obesity to increased risk of type 2 diabetes
Cumulative exposure to obesity could be at least as important as actually being obese in terms of risk of developing type 2 diabetes (T2D), concludes new research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

How much do obesity and addictions overlap?
A large analysis of personality studies has found that people with obesity behave somewhat like people with addictions to alcohol or drugs.

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.

Read More: Obesity News and Obesity Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.