Video: Skinny gene discovered

By contributor
updated 10/1/2007 9:33:32 AM ET 2007-10-01T13:33:32

Janine Geredes is the kind of person many of us love to hate. No matter how much the Northern California woman eats, she never gets fat.

While the rest of us obsess over every morsel passing through our lips, convinced we’ll pack on the pounds if we let our guard down for just one moment, Geredes worries she’ll become unappealingly bony if she doesn’t eat enough.

“I’ve always had to work to keep weight on,” says Geredes, 43, who is 5 feet 6 inches tall and weighs 118 pounds. “When I was a growing up I was teased for being so thin. But now, people are always saying, ‘I wish I could eat like you. You stay so thin. You must work out a ton.’ I don’t.

“My son and daughter are the same way. I’ve always figured it was genetic.”

As it turns out, Geredes may be right.

Scientists now say they have discovered the “skinny” gene. And they’ve found this lucky batch of DNA in a variety of animals, according to a report published Tuesday in the journal Cell Metabolism.

"This gene is in every organism from worms to humans," says the study’s senior author, Dr. Jonathan Graff, an associate professor of developmental biology and internal medicine at the University of Texas Southwestern Medical Center. "We all have it. It's very striking."

Graff and his colleagues had been hunting for a gene that might naturally keep people thin. Eventually, they turned up a promising candidate in a gene that controls fat formation.

Svelte flies rediscovered
And in an interesting twist, Graff notes that this gene was originally discovered by a graduate student at Yale University more than 50 years ago. The student, Winifred Doane, was studying fruit flies and noticed that some were particularly fat while others were quite skinny. Doane, now a professor emeritus at Arizona State University, traced the differences in fly fitness to a single gene that she named “adipose.”

But after publication, Doane’s study languished and was forgotten until Graff started searching for more information on the gene that had caught his attention.

Graff borrowed some of the descendents of the skinny fruit flies from Doane to take a closer look at their genetics. Sure enough, fruit flies with efficient copies of the adipose gene were very thin. Those with poorly functioning copies were pudgier.

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If there was one good copy and one bad one, the flies were medium weight.

“The gene was more like a volume control rather than an on/off switch,” Graff says.

Graff and his colleagues wondered how good copies of the gene would impact survival in the wild. So they subjected the skinny flies to famine-like conditions. Not surprisingly, they did poorly. From an evolutionary perspective, this gene is the one that helps animals do well in affluent times — very much like the situation in western countries today, says Graff.

“In times of plenty, these super skinny, sleek and fast flies can easily get away from predators,” Graff adds. “But in times of shortage, they don’t make it.”

The Texas scientists next wanted to know whether the gene worked the same way in more complicated animals. After proving that they could make worms fat by deleting the adipose gene, the researchers turned their attention to mammals.

First they experimented with single cells in a test tube. When the gene was deleted from ordinary cells, they transformed themselves into fat cells. The cells actually became plump as they accumulated fat droplets, Graff says.

Mice engineered to have efficient versions of the adipose gene were much sleeker than normal counterparts. In fact, they had one-third the body fat of wild mice, says Graff.

Biology of a supermodel
“That would be a big difference in humans,” he explains. “The average woman has about 25 percent body fat. Reducing that by a third would take her down to about 9 percent. That’s super lean — a supermodel kind of thin.”

Obesity experts say the new results are exciting.

“This is so cool,” says Dr. Louis Aronne, a clinical professor of medicine and director of the Comprehensive Weight Control Program at New York-Presbyterian/Weill Cornell Medical Center in New York City.

Theoretically, Aronne says, you might be able to come up with an obesity treatment that mimics what this gene does.

It would be interesting to look at this gene in populations prone to obesity, like the Pima Indians, adds Eric Ravussin, a professor at the Pennington Biomedical Research Center in Baton Rouge, La. Earlier research by Ravussin showed that the Pimas, who live in Arizona and Mexico, become obese only when they live in an environment where food is plentiful and exercise lacking.

Like the beginning of any big advance, the research prompts as many questions as it answers, both experts say.

This gene appears in cells all over the body, Ravussin says. This means that scientists will need to carefully look for side effects when they change levels of the gene or the protein it encodes.

Still, Aronne says, the new study “emphasizes how much closer we are to unraveling the mysteries of body weight regulation.”

But that doesn’t mean people should wait for a pill to cure obesity, he adds. That’s a long way off, even with the new research.

Linda Carroll is a health and science writer living in New Jersey. Her work has appeared in The New York Times, Newsday, Health magazine and SmartMoney.

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