Beer Belly Biology

Researchers identify an enzyme that tells fat to find a home in your abdomen

THURSDAY, Dec. 6, 2001 (HealthDayNews) -- Homer Simpson might not know an enzyme if it bit him in the buttocks, but a form of the important molecule might explain his beer belly.

Researchers in Boston and the United Kingdom say they have identified an enzyme that encourages body fat to stack up in your midsection. The finding, which is limited to mice so far, could help scientists develop new drugs for obesity that would target the molecule. A report on the work appears in tomorrow's issue of Science.

The discovery "points to a very new and not previously suspected mechanism to cause the distribution of fat that we know to be the most dangerous medically; that is the abdominal fat," says Dr. Jeffrey S. Flier, of Beth Israel Deaconess Medical Center in Boston. "And it seems very likely that an inhibitor of this enzyme would be a very useful treatment for people with certain kinds of obesity."

The research examined a phenomenon called "visceral" obesity, abdominal weight gain that gives people an apple-like appearance, as opposed to the "pear-shaped" body type, in which pounds also build up in the buttocks and thighs. Viscerally obese people are prone to a variety of health problems, including weight-related diabetes, heart disease and high blood pressure.

In the latest work, Flier and his colleagues in the United States and Edinburgh, Scotland, focused on the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1). This substance is present in fat cells, where it spurs the production of the hormone cortisol. Along with inciting the "fight or flight" response, too much cortisol in fat cells has been linked to the buildup of abdominal bulge.

Flier and his colleagues created a strain of mice that overproduced 11 beta HSD-1 in their fat, corresponding roughly to what's seen in the fat cells of obese people.

When fed a low-fat diet, the mice with extra amounts of the enzyme initially gained weight the same as their genetically normal cage-mates. However, after about two months, they began to put on the pounds, well, ounces. By the time they reached 15 weeks, they were about 16 percent heavier, on average, than the other animals. The difference was even greater when the mice were fed high-fat meals.

Physical exams showed the added padding was clustered around their middles. In addition, X-ray scans revealed that mutant mice on the low-fat diets had the same body fat profile as normal mice who ate high-fat food. What's more, the genetically altered animals also developed diabetes and high blood pressure and had abnormally high blood fat levels, while the other rodents stayed healthy.

The next step, Flier says, is to find out why some people amass mass in their bellies while others do not.

"We don't really know what is driving the enzyme in humans to be increased," he says.

Susan K. Fried, a fat expert at Rutgers University who is familiar with the study, calls the work "really cool."

"The fact that you can make one fat depot grow more than another is really interesting," she says. "There seem to be different types of fat cells that have different biochemical features."

The notion that a drug could target 11 beta HSD-1 is "nice," she adds, although it would have to be tweaked to avoid interfering with the enzyme in other tissues.

However, Flier says other research in mice missing 11 beta HSD-1 suggests that partially blocking its action wouldn't hurt, and could benefit other organs, including the brain.

What To Do

To learn more about obesity and its many associated health problems, check out the American Dietetic Association or the University of Pennsylvania.

For more on weight-related diabetes, try the American Diabetes Association.

SOURCES: Interviews with Jeffrey S. Flier, M.D., Beth Israel Deaconess Medical Center, George C. Reisman Professor of Medicine, Harvard Medical School, Boston; Susan K. Fried, Ph.D., professor, nutritional sciences, Rutgers University, New Brunswick, N.J.; Dec. 7, 2001, Science
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