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Old Mon, Jul-21-03, 11:29
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gotbeer gotbeer is offline
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Default "2 genes found to stop fat cells from forming"

2 genes found to stop fat cells from forming

One might explain body shape; the other may help block obesity

07/21/2003

By SUE GOETINCK AMBROSE / The Dallas Morning News


link to article

America is getting fatter, not thinner. So it might seem surprising that the body actually has a way to prevent fat from forming.

But last week, two teams of scientists one from Dallas and one from New York reported on two genes that seem to keep fat cells from developing. The findings could someday point to new ways to combat obesity.

Understanding what controls whether or not fat cells develop could also explain why extra pounds end up on the hips and belly, and not everywhere else.

Scientists at the University of Texas Southwestern Medical Center at Dallas studied a gene called insig-1, and found that it blocks the formation of new fat cells. The scientists suspect that the gene is more active in some areas of the body than others.

"Maybe the contour of your body is based on" this gene, says Roger Unger, the UT Southwestern scientist who led the study. "When you overeat, you get fat in certain places and not others. You don't get fat on the bridge of your nose and the back of your hand."

In other work, researchers at The Rockefeller University in New York focused on a gene called Foxa-2 and found that it also prevents immature cells from developing into new fat cells.

"Both papers describe a mechanism which puts the brakes on obesity," says Rockefeller's Markus Stoffel.

One of the genes, insig-1, was discovered in 1997. Last year a team of Dallas scientists led by Nobel laureates Joseph Goldstein and Michael Brown found that the gene could influence cholesterol production. That discovery led to the idea that the gene might also influence fat storage.

UT Southwestern's Dr. Unger and his colleagues showed that when the insig-1 gene is inserted into immature fat cells, it prevents the cells from maturing. The study was published online last week in the Proceedings of the National Academy of Sciences.

It may be that the gene is active in these immature cells in some parts of the body but not others, Dr. Unger says. Where the gene is more active, the theory goes, fat cells are less likely to develop.

Rockefeller's Dr. Stoffel says that while both genes seem to block the development of fat cells, they probably do it in different ways. More experiments would be needed to see whether the two genes work together. But right now, Dr. Stoffel says, the evidence indicates that the Foxa-2 gene is part of a natural defense mechanism against severe obesity.

As the Rockefeller scientists reported last week in the Journal of Clinical Investigation, mice with a faulty copy of the Foxa-2 gene gain weight more quickly than normal mice when fed a high-fat diet. That's because the gene can't slow the development of new fat cells as effectively as it does in normal mice, Dr. Stoffel says.

Even so, he says, it's obvious that the gene isn't that effective in preventing obesity. If it were, mice wouldn't get as fat as they do.

Still, he says, if doctors could figure out how to make the Foxa-2 gene more active, it might help slow weight gain.

Other researchers on the Dallas team were Jinping Li, Kiyosumi Takaishi, William Cook and Sara Kay McCorkle.

E-mail sgoetinck~dallasnews.com
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