What hormones are released that cause you to feel full after eating?

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August 8, 2002, Section A, Page 21Buy Reprints

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Scientists have identified a hormone that causes the sensation every dieter craves: the feeling of fullness.

The hormone, Peptide YY3-36 or PYY, is made by cells in the small intestine in response to food and then circulates to the brain, where it switches off the urge to eat.

''It stops you feeling hungry,'' said Dr. Stephen R. Bloom, a professor of endocrinology at Hammersmith Hospital at Imperial College School of Medicine in London, who led a study of the hormone that was being published today in the journal Nature. ''It controls you and me after every meal we eat.''

PYY has been known since the 1980's, but its ability to suppress appetite was discovered only within the past year or so, Dr. Bloom said.

In his study, people who were given a tiny dose of the hormone and offered a buffet lunch two hours later consumed about 33 percent fewer calories than they did when they were not taking the hormone. They reported feeling full, but not overstuffed or ill. The effects lasted about 12 hours, and when the hormone wore off, the people had no tendency to overeat to make up for the calories they had missed.

Dr. Bloom said he hoped it would be possible to use PYY itself, a drug based on it or a diet that stimulates the body to make more PYY to help people lose weight. High-fiber diets seem to stimulate PYY production naturally, he said. Pure PYY would have to be injected; it cannot be taken by mouth because it would be broken down in the stomach. But a drug based on PYY might be made in pill form, he said.

The research is in its earliest stages; today's study included only 12 people, none of them obese. Far more testing is needed to find out whether PYY or related molecules are safe and effective, especially for long-term use. Another appetite suppressant, leptin, made by the body's fat cells and thought to have promise in treating obesity, has turned out not to work because most overweight people are resistant to it.

A researcher who was not involved in the PYY study, Dr. David E. Cummings, an endocrinologist at the University of Washington and the Department of Veterans Affairs in Seattle, said, ''I think this is a very important finding.''

Dr. Cummings said PYY might ultimately prove more useful than other hormones previously found to suppress appetite. Some of those hormones suppress appetite only briefly, so that test animals eat smaller meals, but compensate by eating more often, and so do not lose weight. Others, like leptin, affect weight, but only after a very long time, he said.

PYY seems to fall in the middle. ''It fills a new niche,'' Dr. Cummings said. ''It rises with every meal and falls in a few hours, but its actions are longer lasting.''

In animals, he added, PYY keeps working with repeated doses and causes weight loss.

In May, Dr. Cummings led a team that showed that another gut hormone, ghrelin, was a powerful appetite stimulant. He said that PYY seemed to be an ''anti-ghrelin'' and that, to help people lose weight, adding PYY would probably work better than trying to take away ghrelin.

Drugs to help people lose weight are badly needed, Dr. Bloom said, because obesity is increasing worldwide in every age group.

''It's causing a lot of disease,'' Dr. Bloom said. ''It's the biggest epidemic that exists, and it causes far more premature death than any other disease.''

Globally, a billion people are obese. In the United States, about 60 percent of adults are overweight or obese, as are nearly 13 percent of children. Some 300,000 Americans a year die from illnesses caused or worsened by obesity.

Dr. Bloom said he thought PYY would be safe, with few or no side effects, since it is made by the body and people are exposed to it after every meal. In addition, the dose that quelled appetite in his study was small, only about as much as the body makes after a generous meal.

''Side effects?'' he said. ''You must be having them every day when you eat lunch. Did you notice them yesterday or today? I can't think of anything more natural than something that goes up after a meal.''

But some of Dr. Bloom's co-authors on today's paper did have concerns about potential side effects. Dr. Michael A. Cowley from Oregon Health and Science University in Portland said that although no problems had occurred, PYY might act on the cardiovascular system and gut. Dr. Cowley added that large doses could theoretically affect heart rate and blood pressure or cause digestive problems like diarrhea.

''We're just saying you have to be very careful,'' he said.

PYY is easy to synthesize in a laboratory and not terribly expensive, Dr. Bloom said.

It costs about $250 per milligram, Dr. Cowley said, enough for three treatments. But that does not include the costs of testing and marketing it as a drug, which would run to hundreds of millions of dollars. Dr. Bloom said he was not sure whether drug companies would be interested in developing PYY itself, because, as a naturally occurring molecule, it might not be patentable. A new molecule related to PYY would be patentable, though.

Like many other scientists, Dr. Bloom attributed the rise in obesity to the increased availability of fattening foods. Humans had evolved to survive famine, not feast, he said, and people today are the descendants of ancestors who had withstood starvation because they had genes that enabled them to store fat as a reserve.

''We didn't evolve for this environment of supermarkets at every street corner,'' Dr. Bloom said. ''So what we do is, we find out how appetite is regulated and we work to readjust that regulation to make us more fitted to the environment we're in. We interfere with nature to alter the bad effects of this environment for which we haven't evolved.''