Researchers Identify ‘Fat Gene’ That Slows Body’s Use of Calories

For the second time in less than a year, researchers have pinpointed a genetic flaw that makes people fat.

Three international teams of researchers reported Thursday that they have identified a common defect in a gene that regulates how fast the body burns calories. Those with the bad gene tend to grow potbellies and develop diabetes earlier in adulthood.

Other scientists recently reported the identification of a gene, and, two weeks ago, the so-called ob protein produced by the gene, that controls appetite, thereby regulating how many calories an individual takes in. The latest find, in contrast, is a gene that works at the opposite end of the metabolic cycle, governing how fast the body burns up the calories it consumes.

Like the identification of the appetite-regulating protein, the discovery may quickly yield new ways to fight obesity. Several drug companies, aware that scientists suspected a genetic connection, are already testing medicines intended to circumvent the flaw by stimulating the body to get rid of calories faster. It should also become possible soon to use a simple blood test to identify those who have the gene.

The gene contains the blueprint for a crucial bit of biological equipment called the beta-3 adrenergic receptor. It is part of the chemical machinery that regulates metabolism--the rate at which the body uses calories and stores fat.

And although a defective form of the ob gene has not yet been observed in humans, the beta-3 adrenergic defect is apparently quite common, appearing in 12% of Caucasians and 25% of African Americans and Hispanics. The gene was present in 54% of Pima Indians, a tribe with an unusually high incidence of obesity and Type 2 diabetes.

“We believe this to be the first mutation in a human gene that influences obesity and adult-onset diabetes,” said Dr. Alan R. Shuldiner, a Johns Hopkins scientist who led one of the research teams. “People with the mutation are more obese, have lower metabolic rates and get diabetes at younger ages.”

The newly discovered defect “probably by itself does little,” said Dr. Bradford Lowell of Beth Israel Hospital in Boston. “But in association with other yet-unidentified factors, it is probably what produces the genetic component of obesity.”