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Chemical In Brain Is Most Potent Appetite Stimulant Ever Found

October 22, 1985 GMT

DALLAS (AP) _ A chemical previously identified in the human brain has been found to be the most potent appetite stimulant known, and researchers say it could play a critical role in binge eating, anorexia and other eating disorders.

When the chemical was injected into the brains of rats, they began overeating within minutes and by the third day were eating more than twice what they would normally consume, said Sarah Leibowitz, a neurobiologist at The Rockefeller University in New York.

The rats’ daily weight gain was more than four times their normal gain during 10 days of testing, according to Leibowitz and Glenn Stanley, a researcher in her laboratory.

Leibowitz reported the findings Monday at a meeting of the Society for Neuroscience.

Leibowitz said the substance, called neuropeptide Y, could be responsible for the binge eating attacks experienced by people with the eating disorder bulimia, and for occasional overeating in normal individuals.

In patients with anorexia, who fail to eat, neuropeptide Y could cause the periodic, erratic binges that have been observed, she said.

Scientists say 5 percent of Americans, mainly young women, suffer from bulimia or anorexia, both of which can be fatal.

Neuropeptide Y causes a craving for carbohydrates, the food groups that includes many snack items and sweets favored by binge eaters, Leibowitz said.

Researchers believe that in normal rats, it builds up before the first meal of the day and presumably helps ensure that the rats get adequate nutrition at that meal. Leibowitz believes that neuropeptide Y also builds up in humans during the night, and partly governs their appetite in the morning.

The chemical is one of perhaps dozens of naturally occurring substances that either suppress or stimulate appetite, she said. One of the first of those to be discovered was cholecystokinin, or CCK, a powerful appetite suppressant.

Ten years ago, James Gibbs and Gerard Smith of New York Hospital-Cornell Medical Center in White Plains, N.Y., discovered that CCK in the intestine was a potent appetite suppressant, triggering a search by drug companies for a new diet drug.

CCK itself cannot be given as a diet pill, because it is broken down in the digestive tract, Leibowitz said. But drug makers hope to develop a chemically similar drug that is not broken down, she said.

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Whether CCK actually produces a feeling of fullness, or somehow disturbs the digestive system to reduce appetite, remains open to debate, researchers said. But in a symposium Monday, researchers said it now appears that CCK also acts directly in the brain as an appetite suppressant.

Both CCK and neuropeptide Y are believed by some researchers, among them Leibowitz and Bartley Hoebel of Princeton University, to act on a portion of the brain called the paraventricular nucleus, located in the hypothalamus - a structure at the base of the brain that governs eating, drinking and certain hormones.

Leibowitz and Stanley believe that neuropeptide Y works in concert with a substance called norepinephrine. The substances have previously been found to coexist in the human brain, and norepinephrine is also known to stimulate carbohydrate cravings.

It is one of the so-called neurotransmitters that brain cells use to communicate. (Neuropeptide Y may also be a neurotransmitter, Leibowitz said.)

Neuropeptide Y is too new to have been studied yet in humans, but researchers have found that norepinephrine is decreased in people with anorexia. That suggests that neuropeptide Y is also decreased, possibly explaining why people with anorexia don’t eat, Leibowitz said.

A further piece of this appetite control system was put into place by Richard Wurtman of the Massachusetts Institute of Technology, Leibowitz said. He found that the consumption of carbohydrates - presumably under the influence of neuropeptide Y and norepinephrine - indirectly causes the production of yet another brain chemical called serotonin that turns off the manufacture of neuropeptide Y, thus turning off the carbohydrate craving.