Trigger for Obesity Identified

Finding could lead to new drug therapies, researchers say

MONDAY, Nov. 21, 2005 (HealthDay News) -- Gaining weight from overeating is a problem faced by many adults, and now scientists have apparently discovered one reason why.

In experiments with rats, researchers found that the hormone leptin, which helps burn fat in fat cells called adipocytes, becomes ineffective, allowing for weight gain from overeating.

"The cells that make leptin are fat cells -- the cells that store the fat," said lead researcher Dr. Roger H. Unger, a professor of internal medicine and director of the Touchstone Center for Diabetes Research at the University of Texas Southwestern Medical Center at Dallas.

This dichotomy has led to a question that's only now being answered, Unger said. "Why would cells that have as their main function fat storage produce a hormone that would prevent fat storage by burning up all the fat?" he said. "How is it possible that these cells produce a fat-burning hormone, and yet store a huge amount of fat?"

Unger's team found that when rats are overfed and made obese, the receptor for leptin, which makes fat burn up, disappears from the fat cell. "So the leptin produced by the fat cell will not come back and act on the fat cell," Unger said. "That way the cell can be smothered by leptin, but the leptin can't work."

There is an evolutionary reason for this, Unger said. "We think of obesity as bad, but in fact throughout evolution, obesity is the only way we survived famine. The people who were most efficient in storing fat were the people who survived," he said. "Obesity is nature's way of surviving famine."

The new research appears in this week's online edition of the Proceedings of the National Academy of Sciences.

In another experiment, the researchers overfed genetically altered rats that couldn't lose the leptin receptors in their fat cells. "We make these animals overeat, but they don't lose the leptin receptor on the fat cells," Unger said. "When that happens, they can't get fat, because the leptin is acting on the fat cell burning up the fat."

The key to preventing obesity is to prevent the loss of the leptin receptor on the fat cell, Unger said. His team is continuing its research with humans, where early results appear similar to what was found in rats.

Unger believes that researchers could one day use this information to invent a drug that would prevent leptin receptors in fat cells from disappearing.

There's an easier way to prevent obesity, however, he said: "Just don't put so much food into your mouth. It is questionable to use this finding as a substitute for willpower."

But one expert thinks these findings are an important breakthrough in understanding obesity.

"Although obese people produce a lot of leptin, somehow they don't stop eating," said Dr. Julio Licinio, a professor of psychiatry and biobehavioral sciences and endocrinology at the David Geffen School of Medicine, University of California, Los Angeles.

Before you can develop drugs to treat obesity, you have to understand what makes people become obese, Licinio said. "This paper shows a mechanism for the inactivation of leptin. This is really a big breakthrough, because understanding this mechanism could really lead to new treatments for obesity."

More information

The U.S. Weight Control Information Network can tell you more about obesity.

SOURCES: Roger H. Unger, M.D., professor, internal medicine, and director, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas; Julio Licinio, M.D., professor, psychiatry and biobehavioral sciences and endocrinology, and director, Center for Pharmacogenomics and Clinical Pharmacology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles; Nov. 21-25, 2005, Proceedings of the National Academy of Sciences
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