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New Appetite Hormone Is to Diet For

Cuts food intake by one-third, research shows

WEDNESDAY, Aug. 7, 2002 (HealthDayNews) -- It's the buffet owner's dream come true: A hormone that cuts all-you-can-eat by one-third.

Injections of the substance, a gastric protein called PYY3-36, significantly trim appetite and food intake in rodents and people, according to a new study by English, Australian and American researchers.

PYY, which acts on an area of the brain that both stimulates and reduces the urge to eat, adds to a growing menu of hormones involved in energy balance.

By manipulating these molecules, experts hope one day to offer obese people an effective chemical diet to help them shed pounds. However, since the first of these compounds, leptin, was discovered in the mid-1990s, that effort has been largely frustrated by disappointing results in clinical studies.

A report on the latest findings appears in this week's issue of the journal Nature.

Leptin belongs to a group of long-acting hormones that regulate energy intake. Others, like the recently discovered ghrelin, work on a much shorter time scale. PYY falls somewhere in the middle, its effects lingering for roughly 12 hours after a surge in response to eating.

The hormone is released by the stomach and intestines after a meal, in proportion to how many calories -- and, importantly, what kind of nutrients -- are eaten. It then wends its way to a small corner of the brain called the arcuate nucleus. This center serves as a telegraph desk, relaying chemical signals of hunger and satiety deeper into the mind, and helping stimulate the secretion of hormones from the pituitary gland as needed.

In the new study, Rachel Batterham, of Imperial College in London, and her colleagues sought to learn what would happen if they tried to augment the natural PYY system with a synthetic form of the substance.

They first injected the hormone into rats and mice, and saw that the animals greatly cut back their food intake and gained less weight over time. The effects on appetite of the substance occurred even in rodents that hadn't eaten for a day. However, PYY injections didn't affect appetite in mice genetically engineered to be lacking a brain receptor that recognizes the hormone.

Next, the scientists infused PYY -- at doses designed to mimic what's secreted after a meal -- into 12 men and women with healthy body weights who were then turned loose on an unlimited buffet with no time limit for grazing.

Compared with volunteers who received saltwater injections, those who received the hormone ate one-third less, on average, and reported feeling about 40 percent less hungry. Even so, they had no greater sensation of fullness or nausea and drank the same amount of fluids, all of which can influence food intake.

Food diaries kept by the subjects revealed that the reduced appetite remained for 12 hours, after which intake returned to normal.

Michael Cowley, a scientist at the Oregon National Primate Research Center, in Beaverton, and a co-author of the study, said the results warrant a closer look at PYY -- this time in obese people.

Cowley's colleagues in England are now embarking on just such a study, while his group in Oregon will be analyzing the hormone's effects on gluttonous monkeys.

"The receptors for PYY are expressed throughout the body, so you have to be cautious," Cowley said. But none of the volunteers in the latest study showed adverse reactions to the substance, so it appears to be relatively safe so far.

Cowley, like other appetite experts, isn't ready to claim that obesity will succumb to drugs. "There's no magic bullet," he said, not even hormones.

One reason for this fact -- dismaying as it may be to people hoping for such a treatment -- is precisely because the list of appetite regulators is steadily growing.

"It's quite difficult when you have all these pathways that overlap," said Dr. Joel Elmquist, an endocrinologist at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. Blocking one may merely lead to more activity in another.

After all, Elmquist said, "of all the evolutionary pressures, adequate food intake and [body fat] is probably one of the strongest. Mammals are especially good at maintaining their body weight."

Even if doctors eventually find a safe, effective weight loss hormone, Cowley added, there's no substitute for eating a modest amount of calories and exercising.

More than six-in-10 American adults are overweight, as are one-in-seven children and adolescents, according to the U.S. Surgeon General. Unhealthy weight accounts for 300,000 deaths a year in this country.

What To Do

For more on the problem of obesity, visit the U.S. Surgeon General online or the National Heart, Lung, and Blood Institute.

SOURCES: Michael Cowley, Ph.D., assistant scientist, Oregon National Primate Research Center, Beaverton; Joel Elmquist, DVM, Ph.D., associate professor of endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston; August 8, 2002, Nature
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