- The Washington Times - Monday, January 26, 2004

A University of Florida study suggests that dieters who persevere in losing weight may be helped by a “slimming hormone.”

The study of rats, published in the current issue of the monthly journal Obesity Research, showed that adult rats fattened on high-calorie foods returned to their lower weights when scientists used gene therapy to produce the hormone, called leptin, in the rodents’ brains.

All mammals, including humans, produce leptin in their fat cells, said Satya Kalra, a neuroscientist at the University of Florida College of Medicine, who led the study funded by the National Institutes of Health. He said the hormone signals the brain to reduce appetite and burn calories.

Researchers believe that in some cases of obesity there is a “leptin insufficiency” in the area of the brain called the hypothalamus, Mr. Kalra said in a telephone interview yesterday. Ironically, that insufficiency may occur because obesity leads to overproduction of leptin.

Much of his work has focused on a tiny section of the hypothalamus known as the paraventricular nucleus. “Most of the data [from previous research] indicates that the paraventricular nucleus is one of the most important targets for action of neurotransmitters that stimulate or inhibit appetite and also [for] the neural circuits that increase energy expenditure,” Mr. Kalra said.

He stressed that no one is predicting the “slimming hormone” alone will be a quick and easy fix for the nation’s obesity epidemic, which is a major contributor to medical problems such as heart attacks, strokes and diabetes. Nearly 59 million Americans are considered obese.

Mr. Kalra noted a drawback, which a University of Florida press release described as a “caloric Catch-22” associated with leptin: Overweight mammals produce too much of it. In fact, Mr. Kalra said, they produce so much of the hormone that it thwarts the very mechanism that should eliminate excess fat — a phenomenon known as leptin resistance.

“For reasons unknown, when leptin levels are increased in the blood, [leptin is] ineffective in performing its normal function,” said the researcher. “It increases more quickly if the animal consumes a diet that’s very rich in calories.”

Leptin resistance affects up to 95 percent of dieters, said Tamas Horvath, a leptin specialist who heads reproductive neuroscience at the Yale University School of Medicine.

Mr. Kalra said the results of the study suggest leptin eventually could provide better weight-control methods either through gene therapy or new drugs, but he predicted human applications are years away.

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