Eating fatty foods, not exercising and somehow remaining lean and healthy--it's the couch potato's dream. And for a certain group of genetically altered mice, it has now become a reality. According to a report in the October issue of the journal Nature Medicine, Washington University researchers have developed mice that resist obesity and diabetes despite eating a diet high in fat. The key, it appears, lies with a protein dubbed uncoupling protein-1, which when produced in muscle tissue mimics the effects of exercise.

Food energy is converted into a chemical energy called ATP, which fuels the body's muscles during exercise. In the absence of exercise, ATP serves to make and store fat. Accumulation of this fat can lead to obesity, which in turn can lead to diabetes. The new study showed that in mice whose skeletal muscle was genetically coaxed into producing uncoupling protein-1, the protein converted the food energy into heat, instead of ATP. So although these mice were consistently eating poorly, they stayed as trim and fit as mice that were fed a low-fat diet. Unaltered mice fed the high-fat diet, in contrast, became obese and diabetic, and exhibited high cholesterol levels.

Researchers hope to soon determine whether gene therapy can not only prevent but reverse obesity and diabetes in animals. Similar treatment may one day help humans. "It may be possible, either through drugs or gene therapy, to turn on something like uncoupling protein that would waste energy instead of storing it in fat," says team member Clay Semenkovich. "Such treatments would promote leanness.