Couch Potato's Delight

SAN FRANCISCO--Like switching on a miniature furnace in the body, scientists have created a compound that spurs certain fat cells to burn up calories without forcing them to endure jogging, swimming, or biking. The chemical, described here today at the annual meeting of the American Chemical Society, raised the metabolic rate of rats by 30%--equivalent to a weight loss of nearly 3 kilograms per month in people. But it may take several years before the potential drug reaches the market, and even when it does, researchers caution that it won't be a "magic pill" for slenderness.

The compound mimics adrenaline, the hormonal messenger of the "fight or flight" response to danger. One type of adrenaline receptor starts the heart beating faster, and a second dilates blood vessels and lowers blood pressure. In 1989, a third receptor--the so-called beta_3 adrenergic receptor--was discovered on brown fat cells, which convert fat into heat. A potential adrenalinelike drug for weight control must target only the fat-cell receptors to avoid dangerous side effects in the cardiovascular system.

A team led by Robert Dow of Pfizer in Groton, Connecticut, studied the beta_3 receptor to see what makes it unique. After homing in on a region made of carboxylic acid, they tinkered with adrenaline to get a version that binds only to the receptor. They added the modified adrenaline compound, called CP-331679, to cultured human fat cells, and saw that the beta_3 receptors were activated and were triggering a biochemical cascade inside the cell. Next, they fed the compound to rats and tracked the animals' oxygen intake, an indirect measure of the metabolic rate of the fat cells. Over several hours, the rats consumed 30% more oxygen than control rats; the experiment was not designed to test for weight loss.

Obesity experts are encouraged that the compound so potently stokes the furnaces of brown fat cells. "That's a great step forward," says Xavier PiSunyer of Columbia University Medical School. However, he points out, many hurdles remain, including the fact that human fatty tissue has few brown fat cells. To work in people, normal fat cells will have to respond to the drug, too.

If the drug were to pan out in clinical trials, it would probably be prescribed as part of a regime including diet change and exercise, says Dow, who stresses that the drug is unlikely to be a magic bullet. "The idea of a pill to cure obesity is probably not going to come to be," he says.

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