Salk News: Researchers find obesity receptor

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

Contact: Robert Bradford
Salk Institute

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