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Natural System Puts Brakes on Fat Gain

July 15, 2003 -- Fat people would be much fatter without Foxa-2. The gene puts the brakes on fat gain, mouse studies show.

It also helps the body respond to the hormone insulin. Poor insulin response -- known as insulin resistance -- is a major milestone on the road to diabetes.

Now the trick is to find a way to turn the gene on in people at risk for developing obesity, says study leader Markus Stoffel, MD, PhD, of Rockefeller University in New York. Stoffel and colleagues report the findings in the Aug. 1 issue of the Journal of Clinical Investigation.

"We have shown that Foxa-2 has two beneficial effects in mice," Stoffel says in a news release. "This is the ideal combination for pharmacologically treating obese or type 2 diabetes patients, or people with a risk of developing obesity."

Foxa-2is unlike other known genes linked to obesity. The new findings mark the first time anyone's found a gene that's turned on in fat cells themselves to counteract obesity.

The gene isn't on all the time. In mice, it waits until the animal already is overweight. Then it kicks in. It keeps young cells from turning into fat cells. And it slows down further fat production and storage in mature fat cells.

The researchers think the same thing happens in people.

Interestingly, the researchers found that growth hormone turns on Foxa-2 in cells that don't normally express the gene. That, they suggest, is why growth hormone has anti-fat effects. But they warn against the use of growth hormone to lose weight.

"We do not believe that growth hormone is responsible for the induction of Foxa-2 in obesity," Stoffel says. "And we can't give growth hormone to patients because there are too many negative side effects."

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