Scientists Seek 1 Pill to Make You Smaller

Feeling famished? Or so full you couldn't eat another bite? It may be all in your head.

Research has shown when it comes to appetite, certain hormones, enzymes and genes all play a role in signaling the brain when it's time to eat. Understanding how these mechanisms interact is a key pursuit in the United States, where two-thirds of the population is overweight and nearly 59 million are obese.

Keeping the pounds off is also an expensive problem. Researchers at the Center for Disease Control and Prevention in Atlanta recently estimated weight-related health problems cause $93 billion in U.S. treatment costs every year.

"We've been telling people for more than 150 years that in order to prevent obesity, they need to eat less and take more exercise," said Stephen Bloom, a British obesity researcher at London's Imperial College. "And yet the population has gotten fatter and fatter and thousands of people die unnecessarily every week because they overeat. So obviously it doesn't work."

What could work, argue Bloom and others, is fooling the brain into thinking it's full.

The Hungry Hormone

This has certainly been tried before. A popular diet-drug cocktail of fenfluramine and phentermine, known as fen-phen, entered the market and then exited when it was determined it could have dangerous side effects on the heart.

Ephedra, an herbal diet supplement, will soon carry warning labels following the February heatstroke death of Baltimore Orioles pitcher Steve Bechler, who had been taking the supplement. Other pills remain available and carry no warnings, but appear to be less effective as weight-loss aids.

Recently, however, scientists have directed their attention to a small group of hormones and enzymes that, they believe, could play a role in developing a diet wonder drug.

Among the hottest targets are the hormones known as ghrelin and PYY. Japanese scientists discovered ghrelin in 1999 and American researchers proved its role in appetite a year later.

According to work by David Cummings, an endocrinologist at Seattle's Veterans Administration Medical Center at the University of Washington, ghrelin is produced in the stomach and, when delivered to the brain, tells the body to eat — immediately.

What's more, Cummings research showed that obese people who are dieting and losing weight have increased levels of the hungry hormone in their blood. The more pounds they lose, the more their bodies demand they eat more to make up the difference.

By finding a way to artificially reduce the level of ghrelin in the blood, scientists hope to turn off the body's demand to eat.

The ‘Stop Eating’ Signal

Ghrelin appears to have a counterpart — another hormone that sends the opposite signal — telling the brain to hold off the forkfuls.

PYY, which stands for peripheral hormone peptide YY (PYY 3-36), is secreted in the gut and released on a bundle of brain neurons in the hypothalamus that control appetite.

Tests on mice suggest that infusing even small amounts of the hormone into the bloodstream leads to dramatic weight loss. And Bloom and colleagues have shown that tinkering with levels of PYY in people works to suppress appetite.

When his team at Imperial College infused a test group with the hormone they ate a third less food from a free, fancy buffet than people who had received a placebo infusion of saline. Both groups had refrained from eating for a day before the test to ensure they had hearty appetites.

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