New Obesity Gene Discovered

A novel gene that produces a protein called "beacon" plays an important role in the development of obesity and diabetes, says Professor Greg R. Collier. Dr. Collier and his team of researchers at Deakin University in Melbourne, Australia, have found that the protein increases appetite, body weight, and the incidence of type 2 diabetes in desert rats. Because beacon is identical in rats and humans, the beacon gene represents a potential target for the development of anti-obesity drugs, the researchers contend.

Unlike most other animals used in obesity research, the desert rat displays a wide range of body weight and body fat measurements on a standard laboratory diet consisting of 12 percent fat, 63 percent carbohydrate, and 25 percent protein. In the brains of lean and obese rats, the researchers compared gene expression, or production of a specific protein by a specific gene. They discovered a high level of an appetite-stimulating protein that they called beacon in the obese rats and traced it to the new gene. A subsequent search of gene databases found a 100 percent correlation between beacon and a protein found in humans.

The hypothalamus is the region of the brain on which proteins act to control energy intake and expenditure. To test their theory that the beacon gene contributes to the regulation of energy balance, the researchers administered beacon via pumps directly into the brains of lean, nondiabetic rats for 7 days. They found that rats receiving the highest dose, 30 micrograms of beacon per day, increased their body weight by 5 percent by the end of the week. They also found a dose-dependent increase in food intake; those receiving higher doses showed a greater increase in food intake.

To determine how beacon worked to increase food intake and body weight, the researchers looked at the expression of another protein, neuropeptide Y (NPY), in beacon-treated rats. The levels of NPY, known to stimulate appetite, doubled in the rats receiving 30 micrograms of beacon. This suggests that one way beacon increases body weight is to stimulate the activity of NPY.

Next, the scientists compared the effects of treatment with 15 micrograms per day of NPY, 15 micrograms per day of beacon, and a combination of both. While the rats treated with NPY alone ate more and gained more weight than those treated with beacon alone, the rats receiving both proteins showed a significantly greater increase in food intake and body weight than the NPY-treated rats, gaining nearly 10 percent of their body weight over the course of 7 days.

The researchers conclude that beacon may be a new target for the development of therapeutic agents for obesity and anorexia nervosa. Sir George Alberti, president-elect of the International Diabetes Federation, observed that drug research on beacon could proceed quickly because of the precise match between the rat and human beacon genes.

The full report appears in the November 2000 Diabetes, and can be accessed at http://www.diabetes.org/main/professional/journals/default.jsp. s