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Researchers find intestinal hormone curbs eating

A single infusion of an intestinal hormone made people eat less for the rest of the day, regardless of whether they were fat or thin, researchers are reporting today.

The hormone, PYY (for peptide YY 3-36), is of particular interest because it appears to be the intestine's signal of satiety and because overweight people normally make less of it than thin people. Researchers are trying to learn whether some people grow fat because they do not make enough of it and thus get only a weak chemical signal to stop eating.

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In the study, whose results appear today in The New England Journal of Medicine, 24 volunteers, half of them overweight and half of them lean, received PYY or a saltwater placebo at 8:30 a.m. An hour and a half later, they were ushered in to a buffet lunch. On average, those who had received PYY ate 30 percent less.

"It was dramatic," said the principal investigator, Dr. Stephen R. Bloom, a professor of endocrinology at Hammersmith Hospital at Imperial College School of Medicine in London. "We haven't had anyone who didn't get a result."

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The obese subjects ate only 1,810 calories for the rest of the day, compared with 2,456 for those given a saltwater injection. The thin subjects ate 1,533 calories after they had the hormone infusion but 2,312 when they had saltwater.

Bloom emphasized that the findings were preliminary. PYY is an experimental substance; no doctor can prescribe it. And the researchers have not yet tried to find out whether people lose weight if they get PYY infusions day after day. But obesity researchers say the work, which began just two years ago, is encouraging.

"It's part of the moving front of research that's adding new and potentially important molecules into the pathways that control body weight," said Dr. Jeffrey Flier, an obesity researcher who is chief academic officer at Beth Israel Deaconess Medical Center in Boston. There are other promising anti-obesity molecules, he said, but PYY, he added, is particularly intriguing.

"This one has the compelling feature that it's been tested in animals, it's been tested in humans, it seems to work in the same concentrations in obese and lean humans, and the levels in the blood are low in obesity," Flier noted.

Bloom said he began his study of PYY because he is saddened by the obesity he sees every day in his clinic. "Medically, it's a disaster to be obese," he said, adding that the condition exacts social and emotional costs as well: "The rate of suicide is doubled, ... they have a lower average wage, they don't get married. They are unhappy people dying of nasty complications, and it's particularly sad because society tries to blame them."

In the quest for treatments to counter obesity, he went on, "our research team asked the question: what is the best way to restrain appetite?"

The researchers tried filling patients up with water or with bulky, low-calorie foods such as cabbage, without success. When they tried infusing nutrients directly into the bloodstream, the subjects got as hungry as ever.

Bloom concluded that satiation "is neither from the food in circulation after it is absorbed or from the fullness of the gut."

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Those observations led him to PYY, a hormone released by the intestine after a meal. He learned that fat people make less of it than thinner people and that the hormone makes thin people eat less. Rats also eat less when they get it, and they lose weight. Obese people who had gastric bypass operations, which mysteriously result in a loss of appetite, have "sky high" PYY levels, Bloom said.

Researchers have long noted that one reason people find it so hard to lose weight is that the body has many ways to thwart them.


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