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Scientists Discover Reason For Obesity, Adult Diabetes Mutant Gene May Slow Metabolism, Researchers Say

Thu., Aug. 10, 1995

Reassuring the overweight that obesity is more than a matter of sloth and gluttony, scientists have pinpointed for the first time a genetic flaw that makes people fat.

The defect is 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.

The research may quickly yield new ways to fight obesity. Several drug companies 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 identify those who have the gene with a simple blood test.

The gene contains the building instructions 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.

The gene is different from one that has gotten intense publicity in recent weeks. That one, called the ob gene, influences appetite. While a mutant version of the ob gene clearly causes obesity in a strain of inbred mice, no defect in that gene has been found so far in overweight people.

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

Three reports on the discovery, made by Shuldiner and colleagues at Johns Hopkins University, were published in today’s issue of the New England Journal of Medicine.

Experts estimate that anywhere from eight to 30 genes may contribute to obesity. While probably no single gene causes obesity by itself, those who inherit several of them are more likely to have weight problems.

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.”

People who get fat eat more food than their bodies need. Genes influence the desire for food and the way the body uses it. Genes are not necessarily destiny, however. Exercise, the abundance of high-fat food and old-fashioned willpower all play a role in obesity.

Indeed, many skinny people have the defective beta-3 receptor gene, and many fat people do not. The researchers estimate that overall in the United States, it is carried by 12 percent of whites and 25 percent of blacks and Mexican-Americans.

In the newly published work, researchers examined the effects of the gene in people in Finland and France as well as Pima Indians in Arizona, who are especially burdened by obesity and diabetes. In each group, they found subtle but consistent links between the flawed gene and a tendency toward obesity and the adult form of diabetes.


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