Salk News: Researchers find obesity receptor

April 17, 2003

La Jolla, Calif.--A cellular receptor that balances the accumulation of fat and fat burning in the body may be a new target for anti-obesity and cholesterol-fighting drugs, according to a Salk Institute study.

The study, published in the April 18 issue of Cell, identified the function of this key receptor for the first time. The receptor, called PPARd, was found to regulate how fat is used and could point the way to new treatments for obesity as well as its associated lethal medical complications: type II diabetes, cardiovascular disease, hypertension and atherosclerosis.

Professor Ronald M. Evans, the March of Dimes Chair in Developmental and Molecular Biology at the Salk Institute and Howard Hughes Medical Institute investigator, and his team found that stimulating PPARd -- short for peroxisome proliferators-activated receptor -- depleted fat deposits in mice, while mice deficient in PPARd were prone to obesity.

PPARd was shown to regulate the rate by which fat is burned to produce heat or is used to maintain normal cell functions. The process of uncoupling energy from work production to heat generation, known as adaptive thermogenesis, is generally regarded as a physiological defense against obesity.

"We have long known that excess calories are warehoused in fat tissue for future use," said Evans. "We also know that fat is released and consumed in times when energy is needed, such as from exercise or shivering from cold exposure. This study shows us that PPARd is an important regulator of this function. By exploiting PPARd, we hope to design drugs that can control how much fat is stored in the body."

The team found that mice with an activated PPARd gene weighed about 20 percent less than normal mice, even though both groups received the same food at the same rate. Once the mice were a year old, the difference in weight widened, to 35 percent less for the genetically active PPARd mice.

At the same time, activated PPARd protects mice against diet-induced obesity. Mice that had the active PPARd gene did not show significant weight gain over a month's time, despite having a high-calorie, high-fat diet. Mice without the active gene, however, became obese. In addition, a short-term treatment of the obese mice with a molecule that activated PPARd caused a dramatic reduction in fat in their tissues.

"PPARd activates an array of genes that are required for fatty acid combustion and uncoupling, but does not activate genes that are involved in the formation and storage of fats," said Evans. "We show then, that PPARd coordinates fatty acid oxidation (burning) and energy uncoupling to regulate the use of fat."

Obesity is now considered an epidemic in the United States. About 65 percent of Americans are considered overweight, and some states report an obesity rate of over 20 percent of their populations. The condition is strongly linked to some of the leading causes of death in the United States, including high blood pressure, heart disease and diabetes. Deaths due to overweight conditions kill more than 300,000 people a year, second only to tobacco-related diseases, according to the U.S. Centers for Disease Control.
-end-
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

Salk Institute

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.