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A natural fat-buster that made headlines last month for slimming down overweight mice may not do the same for really obese people, new research suggests.

Scientists found evidence that very fat people already have high levels of that substance in their bodies, maybe 20 to 30 times the amount found in slender people.So injecting more may not help at all, says researcher Bradford Hamilton.

But another scientist who studies the substance disagreed, saying the new findings may just mean that the obese need more of the stuff than other people to control their weight.

The substance, called leptin, is produced by fat tissue. Mouse studies suggest it is a messenger to the brain that lets animals keep a relatively constant weight.

The more fat on an animal, the theory goes, the more leptin it produces and the more reaches the brain. If an animal gets too obese, an excess of leptin signals the brain to curb appetite and burn off fat.

Scientists say many processes, biological and social, influence obesity, and leptin is not the total answer.

Last month, scientists reported experiments with mice that were grossly overweight because they could not make leptin. When the animals were injected with leptin, they slimmed down dramatically.

Leptin injections also work in normal mice, said Dr. Stephen K. Burley of the Howard Hughes Medical Institute at Rockefeller University in New York. He is one of the scientists who did the mouse studies.

The new work is reported in the September issue of the journal Nature Medicine. One study came from Hamilton, a Ph.D. candidate at the Sunnybrook Health Science Center in North York, Ontario, and the University of Toronto in Ontario, and colleagues. A second study with similar results is reported by Swedish researchers.

The studies looked at levels of activity of the "obese" gene that makes fat tissue create leptin. The more active this gene, researchers reasoned, the more leptin is being made.

Hamilton and his colleagues compared the gene activity in fat cells taken from 14 extremely obese people, who were more than 70 pounds beyond their ideal weight, with activity in cells from 11 lean people.

They found that the fatter the person, the more active the gene. Apparently the gene is turned on more as fat cells get stuffed with more and more fat, Hamilton said. He estimated that fat people may have 20 to 30 times the amount of leptin that lean people do.

They may be so fat because their brains are not getting leptin's message to slim down, Hamilton said. Leptin would deliver that message by acting on structures called receptors, and maybe receptors in the very fat people are so defective they can't respond, he said.

If so, he said, injecting such people with even more leptin would be futile. "If the receptor is expecting Chinese, it doesn't matter how much you scream at it in English, it's still not going to understand the message," he said.