British scientists find protein that tells brain it's time to stop eating Substance offers promise in treating human obesity


Scientists have found a protein that acts immediately to tell the brain when it is time for the body to stop eating. Rats that received injections of the protein as they nibbled food pellets suddenly appeared satiated and lethargic, as if they had eaten a rodent's equivalent of a big Thanksgiving dinner, researchers said.

It is almost certain that humans have this protein, GLP-1, glucagon-like factor-1, in their brains, the researchers said, since it has been found in identical form in every vertebrate species looked at thus far, from fish to mammals.

The discovery of the protein's role in suppressing appetite comes after the discovery last summer of leptin, a hormone that keeps body weight at a set level, and a report last week that a receptor for leptin had been found in the brain and other parts of the body.

Scientists say these are three pieces to the puzzle of when and how people come to feel full, and they could point the way to effective drug treatments for obesity.

The report on the appetite suppressant is being published in today's issue of the scientific journal Nature. A report of the work on leptin receptors appeared in last Friday's issue of the journal Cell.

The two proteins, which are also hormones, both reduce appetite but in different ways, said Dr. Stephen Bloom, an endocrinologist at Hammersmith Hospital in London, who led the GLP-1 research. GLP-1 acts quickly whereas leptin keeps body weight at a given level over the long term.

The new work is "probably very important," said Dr. Richard Atkinson, director of the Beers Murphy Clinical Nutrition Center at the University of Wisconsin.

Over the years, at least 20 different substances have been found that decrease food intake when injected into animals, he said. Most of these agents work for just a short while because the body has many redundant systems for controlling feeding behavior. The animal starts eating more to counteract the appetite suppressant, he said.

But GLP-1 appears to be different, Dr. Atkinson said, in that it might be a long-sought final pathway for satiation.

Dr. Joel Habener, an endocrinologist at the Massachusetts General Hospital, said that both findings were "really hot leads" in working out the complicated signaling systems by which the body keeps track of when and how much to eat.

Dr. Albert Stunkard, an obesity expert at the University of Pennsylvania, called the new research "tremendously exciting," adding, "It's a whole new ball game."

In a telephone interview, Dr. Bloom explained that GLP-1 was active in the stomach, intestines and pancreas, where it "slows down the absorption of your McDonald's hamburger so you can absorb sugar," Dr. Bloom said.

After a meal it is released from the intestines, traveling into the bloodstream to prompt the release of insulin, which helps metabolize sugar. When GLP-1 is injected into the human body, he said, it produces a gush of insulin like that seen after eating a heavy meal.

"We thought it might also be in the brain," Dr. Bloom said. That led to the experiments being reported today. When rats that have started feeding receive injections of GLP-1 in the brain, he said, they stop eating. They also get less active.

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