Gene Twitching Lets Mice Eat All They Want

They gained no weight and lived longer, study finds

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HealthDay Reporter

THURSDAY, Jan. 23, 2003 (HealthDayNews) -- A mouse experiment raises the tantalizing prospect of fulfilling every glutton's dream -- eating all you want without gaining weight and being healthier to boot.

In the experiment, scientists at the Joslin Diabetes Center in Boston created a strain of mice without one specific gene, which codes for insulin receptors in the fat cells. These FIRKO (fat-specific insulin receptor knockout) mice ate all they wanted -- indeed, they were stimulated to eat more than they wanted -- and did not gain weight, says a report in the Jan. 24 issue of Science.

At 30 months of age, more than middle aged for a mouse, 80 percent of the FIRKO mice were still alive, compared to 45 percent to 54 percent of similar mice who had the gene. And their overall lifespan was increased by 18 percent compared to normal mice who ate as much as they did, the report says.

The key to this marvelous combination of advantages is that the FIRKO mice had fat cells that could not respond to insulin, says a statement by Dr. C. Ronald Kahn, leader of the research team and a professor of medicine at Harvard Medical School, with which the Joslin center is affiliated.

"Since insulin is needed to help fat cells store fat, these animals had less fat and were protected against the obesity that occurs with aging and overeating," says the Kahn statement. "They also were protected against the metabolic abnormalities associated with obesity, including Type II diabetes." That is the kind of diabetes that develops when the body's production of insulin declines with age.

Translating the results to other animals or to people is a major challenge, and it's not known whether the same benefits would occur, the researchers say. They're not talking about genetic engineering. "Perhaps one day if we were able to find a drug to reduce or block insulin action in fat cells in humans, we might be able to prevent obesity, as well as Type II diabetes and other metabolic diseases," Kahn says.

The drug would have to act specifically on fat cells and not on other cells of the body, says Dr. Matthias Blüeher, a doctoral fellow at Harvard Medical School and a member of the research team.

"I think that in the next 10 or 15 years, pharmaceutical companies and independent investigators could develop such a drug," Blüeher says.

The Joslin research team will next look at other animal models "and see if this has an impact on longevity" in them, he says.

The day when the finding can be applied to humans is far in the future, says Wahida Karmally, a research associate scientist at Columbia University and a spokeswoman for the American Dietetic Association, who has been doing studies of a similar fashion.

So people, specifically the more than 80 percent of Americans who weigh too much, should take the obvious non-genetic measures to stay healthy and live longer: Eat less, and eat especially less of fatty foods, Karmally says.

"There have been several recent papers showing that life expectancy increases with weight loss," she says. "But what is more important is the quality of life. Maintaining a healthy body weight, decreasing the amount of fat in the body, decreases the risk of heart disease and diabetes and improves life expectancy and the quality of life."

It is advice to be followed until that magic pill (or gene) is developed, Karmally says.

More information

You can learn about the problems created by obesity and how to avoid them from the National Institute of Diabetes and Digestive and Kidney Diseases, which funded the research. You can also learn about diabetes from the Joslin Diabetes Center.

SOURCES: Matthias Blüeher, M.D., doctoral fellow, Harvard Medical School, Boston; Wahida Karmally, Dr.Ph., research associate scientist, Columbia University, New York City; Joslin Diabetes Center release; Jan. 24, 2003, Science

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