Fanfare over finding first fat gene.

Eight years of genetic sleuthing finally paid off this week for scientists seeking to understand the much studied, much lamented problem of obesity.

For the first time, molecular geneticists have identified and made copies of a gene essential for keeping the body's weight stable. They first tracked the gene down in mice and then used the mouse gene to locate the human equivalent. The genes are an 84 percent match, says Jeffrey M. Friedman of the Howard Hughes Medical Institute at Rockefeller University in New York.

"What you have is a discovery that forms the basis for a new and rational approach to the treatment of obesity," comments Timothy J. Rink, a physiologist at Amylin Pharmaceuticals in San Diego.

Many obesity experts say they know how to get people to diet, lose weight, and want to stay slim, but the body regains those pounds, frustrating everyone involved. With the new gene in hand, scientists can examine why this happens.

"This is a pivotal step in the understanding of body weight," Rink says.

For a century, physiologists have argued about how the body balances food intake against energy use, controlling weight gain and loss. In recent years, some indirect evidence has suggested that fat-laden cells produce a blood-borne messenger that tells the brain to suppress the appetite. But until now, no one could pin down the identity of any satiety hormone.

Then, inspired by the way geneticists had tracked down the mutant gene in muscular dystrophy (SN: 9/7/85, p. 151), Friedman tried the same approach with a strain of mouse called obese. These mice gain up to three times their normal body weight and often develop insulin-independent diabetes.

In this strain, the altered gene probably results in the production of a faulty signaling hormone, Friedman and his colleagues report in the Dec. 1 NATURE. The gene is also defective in another excessively plump mouse strain, but in these mice the gene seems inactive, they note.

Friedman plans to make the gene's protein product next. If it is the satiety signal, it should make obese mice lose weight. Because of similarities between the mouse and human versions of this so-called obese gene, such positive results could bode well for humans seeking help in shedding pounds.

"But it's a long way from cloning a gene to [having] a therapeutic," Rink warns. He and Friedman both emphasize that many other genes -- and proteins -- probably help keep weight stable.

Yet even if these obese mice don't slim down, the discovery should have farreaching effects. "I think it will change the way we think about obesity and the way we do obesity research," says Beverly J. Paigen, a geneticist at the Jackson Laboratory in Bar Harbor, Maine.