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Researchers Report Progress in Fight Against Fat
Date:1/6/2009

Two drugs and a genetic variation are focus of promising studies

TUESDAY, Jan. 6 (HealthDay News) -- Researchers are reporting in two new studies that they seem to be moving closer to the holy grail of new treatments for obesity.

In one study, scientists managed to coax the brains of obese mice to process a hormone called leptin that helps control appetite.

"It's very exciting, because leptin was being talked about as a dead end, that it will never work," said study co-author Dr. Umut Ozcan, assistant professor at Harvard Medical School.

In the other study, researchers gained new insight into a genetic trait that's linked to leanness in skinnier people but seems to make the obese pack on extra weight.

Both studies were published in the Jan. 7 issue of the journal Cell Metabolism.

While there have been advances in the treatment of obesity, it remains difficult for doctors to effectively help fat people lose weight through medication.

Scientists have been studying the hormone leptin since it was discovered in the mid-1990s, Ozcan said. The hormone, which is produced by fat cells, plays a role in controlling appetite.

Some scientists thought that high doses of leptin would force people to eat less by controlling urges for food. But, Ozcan said, it turned out that fat people -- and fat mice -- were immune to the hormone's effects.

"Leptin comes to the brain and knocks on the door, but the brain doesn't hear it," he said.

For the new study, Ozcan and his colleagues found that two existing, FDA-approved drugs could serve as "chemical chaperones" and help leptin gain entry into the brains of mice. The drugs are 4-phenyl butyric acid (PBA), which treats cystic fibrosis, and tauroursodeoxycholic acid (TUDCA), which treats a liver disease.

"They're very safe drugs in humans and used safely for other indications," Ozcan said.

However, he added, there's no guarantee that the drugs would have the same effect in people as in mice. Only studies with humans will resolve that issue.

In the other study, an international team of researchers sought to understand more about a genetic variation that appears to help make thin people slim and fat people obese.

About 12 percent of people have the genetic variation. According to the researchers, a study of mice suggests that people who have the variation are generally skinner than others, but their bodies can go haywire -- and pack on more pounds than they should if they eat a high-fat diet.

The researchers suggested that genetic tests might help determine if people have the variation and, if so, reveal whether they should be concerned about a high-fat diet.

"If one could tell these carriers about the importance of adhering to a healthy lifestyle, the impact would be very significant, and even prolong their lifespan," said study co-author Dr. Johan Auwerx, a professor at the Ecole Polytechnique Federale de Lausanne in Switzerland.

The next step is to try a similar study with people, Auwerx said.

More information

For more on obesity, visit The Obesity Society.



SOURCES: Umut Ozcan, M.D., assistant professor, Children's Hospital Boston and Harvard Medical School; Johan Auwerx, M.D., Ph.D., professor, Ecole Polytechnique Federale de Lausanne, Switzerland; Jan. 7, 2009, Cell Metabolism


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