SCIENTISTS Study Obesity Hormone

Monday, November 5th 2001, 12:00 am

By: News On 6

Treatment with leptin, a natural hormone that helps control body weight, could help many fat people slim down, even if they already have some in their bodies, a new study suggests.

Leptin treatment has already helped people who completely lack the hormone because of a genetic mutation. But only a handful of people don't have any leptin at all naturally.

Results of treatment with other obese people have been disappointing, with only some subjects losing small amounts of weight.

The new work didn't involve treatment. Instead, researchers studied 13 people who had only about half the normal level of leptin because of a genetic glitch. They found that three-quarters of this group was obese, compared to just one-quarter of a comparison group.

That shows that even in people who have some leptin, the amount still affects weight, the researchers said.

``People have been saying it doesn't matter how much leptin you have as long as you have a smidgen. Our research suggests that it does matter,'' said Stephen O'Rahilly of the University of Cambridge, England.

So the work suggests that leptin treatment can help not only those very rare fat people who completely lack the hormone, but also those with low levels, O'Rahilly and his colleagues conclude in the Nov. 1 issue of the journal Nature.

Some experts said it's not clear how many obese people have low leptin levels, although one estimated it could be about 25 percent.

Another scientist said that while the findings involving the 13 people are intriguing because they mirror studies in mice, the study offers no evidence leptin treatments might help a broader category of obese people.

``The trouble is they're trying to generalize from this relatively small group to suggest that many overweight people with low circulating leptin levels could be treated with leptin. It's a leap,'' said Tim Moran, a professor of psychiatry at Johns Hopkins University.

Discovered in 1994, leptin is normally produced by fat cells and is believed to provide a signal about the amount of body fat to the body's energy-regulation system.

In mice, if their brain senses plentiful leptin, indicating lots of fat, it tells the rodents to eat less and be more active. But if there's too little leptin, it signals the mouse to put on weight _ or add fat cells _ in a bid to boost its leptin levels.

Previously, scientists had known that people whose bodies produce no leptin have voracious appetites and become morbidly obese.

The new research offers convincing evidence that people who have leptin at lower than normal levels are also prone to obesity, said Dr. Steven B. Heymsfield of St. Luke's-Roosevelt Hospital in New York, who was not involved in the study.

``The newness of this is that there are partial forms of this condition. It's not an all or nothing situation,'' Heymsfield said.

Heymsfield, who has tested leptin in obese people with mixed results, says an estimated quarter of all obese people are leptin-deficient and could potentially benefit from hormone therapy.

Dr. Rudy Leibel, an obesity expert at Columbia University, said he was intrigued that some of the people in the study's control group did not have genetic mutations yet were obese and had low leptin levels.

Leibel said that suggests there may be as yet unknown problems with their leptin genes or their body's ability to produce leptin. Individuals with such problems might be predisposed to become obese and might benefit from leptin therapy, he said.