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Hormone found to curb appetite in obesity study

A hormone present in every human could hold the key to controlling obesity, British researchers report today, a finding with the potential to reverse an epidemic that is closing in on smoking as the nation's leading cause of preventable deaths.

Scientists at a London hospital gave study participants injections of a hormone called PYY before the participants were allowed to gorge themselves on a lunch buffet that, among other offerings, included chicken curry. Dietitians then measured PYY's stunning effect on appetite: Whether obese or lean, the people who received the hormone ate on average 30 percent less food than those not injected with PYY.

Specialists in the field of obesity research hailed the finding, proclaiming that even though the study included relatively few participants and lasted only a short time, PYY immediately emerges as among the most promising targets for suppressing appetite. But they warned that the body is such an intricate factory of food intake and energy production that it's unlikely any one substance will act as a silver bullet in the battle of the bulge.

"It's an intriguing finding, and it's definitely something that you would want to follow up as a drug target," said Dr. Terry Maratos-Flier, head of the obesity program at Joslin Diabetes Center. "The primary hurdle is that appetite and energy expenditure in humans is regulated by a lot of different factors. So a single target may not be enough -- that would be my cautionary note."

Finding treatments for overweight Americans has never been more urgent. Upwards of two-thirds of all adults weigh more than they should, and obesity is blamed in 280,000 deaths each year.

For years, the mantra against obesity has been eat less, exercise more. But the expanding waistline of the nation proves that strategy has largely failed, and the few scientifically proven drugs to treat obesity either have only mild effects or come from synthetic products with side effects, rather than from naturally occurring agents.

"Most of us are still harping on diet and exercise, but you know that's a tough thing to try to do now. It hasn't worked," said Dr. Caroline Apovian, director of the Nutrition and Weight Management Center at Boston Medical Center. "And there's no end in sight because the obesity rates are still climbing. It might be a viable alternative to look through science and find an antidote to where we've gotten ourselves."

The approach trumpeted in today's New England Journal of Medicine by Dr. Stephen Bloom and colleagues at Hammersmith Hospital in London traces its origins to the discovery of the hormone PYY in pig intestines in 1980. It was years before Bloom's team detected the hormone's role in controlling humans' urge to eat, acting as a sort of stop sign for overconsumption.

In fact, scientists have long employed hormones in the quest to thwart obesity. In the mid-1990s, studies on mice suggested the hormone leptin held great promise for treating overweight patients by reducing their appetites. But researchers discovered that leptin levels in the obese are actually elevated, suggesting they develop a resistance to its appetite-suppressing powers.

PYY appears fundamentally and dramatically different. Bloom established that the obese have reduced rates of PYY and theorized that giving them more of it should reduce their desire to eat.

The British researchers decided to find out what happened if they injected humans with an amount of PYY equivalent to what is released naturally in a lean person after a meal. They had come to understand that PYY is responsible for making humans feel satiated.

They compared the effects of PYY in 12 obese study participants and 12 lean patients, feeding them on two occasions. In the study, half of the participants got a mixture of the hormone and saline and the other half received only saline.

"Lo and behold, when we infused the PYY, people didn't eat so much," said Bloom, a professor of endocrinology at Imperial College London. "We were absolutely amazed that everyone who got the PYY infusion ate much less, 30 percent less. And it was free of side effects and didn't produce any symptoms." The effect persisted, with researchers reporting that for 12 hours after being injected with the hormone, the participants continued to have significant appetite suppression.Bloom acknowledged yesterday that the study included only a small number of participants but said it achieved statistical robustness because of the finding that everyone who received PYY ate less food.The British scientists plan to expand their research in an effort to determine whether taking PYY long-term will achieve a comparable effect. Bloom said they intend later this year to begin a study that would involve giving participants PYY for at least two months, a step that obesity specialists said is pivotal to proving the true potential of the hormone. "There have been other things that have had promise, too, but very few drugs can demonstrate true efficacy over long-term study," said Dr. Andrew Greenberg, director of the Obesity and Metabolism Laboratory at Tufts University. Bloom estimated that it could be at least five years before an injectable version of PYY is ready for the market and as many as 15 years before scientists figure out a way to convert it to the more-desirable pill form.Still, scientists who have spent years attempting to unravel the mysteries of obesity control said the discovery marks a significant moment in that quest."There have been many new molecules and pathways identified in the last few years that influence body weight," said Dr. Jeffrey Flier, an endocrinologist and chief academic officer at Beth Israel Deaconess Medical Center. "This particular discovery about PYY has a very interesting feel to it, with all the elements to conclude that this is a very important player in body-weight reduction."Stephen Smith can be reached at stsmith@globe.com.

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