From the Brains of Rats: Secrets of Skinniness

NEW YORK -- Scientists have identified a powerful appetite suppressor in the brain, a substance that in rats causes them to eat as much as 95 percent less by making them feel full, according to a study published Thursday.


It may be the most potent natural appetite suppressor yet identified in rats, said Dr. Stephen Bloom, a professor of endocrinology at the Royal Postgraduate Medical School in London and a researcher at London's Hammersmith Hospital.


Scientists might need only two years or so to develop a pill for human testing as a way to fight obesity, he said Wednesday.


The substance is called glucagon-like peptide-1, or GLP-1. Scientists knew it existed in the brains of mammals, but they didn't know what it did, Bloom said.


The new work suggests it is a key part of the brain's regulation of food intake. GLP-1 and the brain-cell structures it acts on are found in a part of the brain called the hypothalamus, which regulates appetite and other basic behavior.


While the substance has been tested only in rats, GLP-1 is found in the hypothalamus of people and it acts on similar structures, so Bloom said he is highly certain that GLP-1 has the same role in people.


In a study reported in Thursday's issue of the journal Nature, Bloom and his colleagues injected GLP-1 into the brains of rats. In animals that had not eaten in 24 hours, the injections reduced food intake by up to 95 percent, depending on the dosage.


A rat injected with GLP-1 "behaved like any animal does after it has a meal," Bloom said. "It gets sleepy, it grooms itself, it doesn't move around so much." That shows GLP-1 was cutting appetite by making the rats feel full rather than sick, he said.


Scientists also tested a substance that blocks the effect of GLP-1. The blocker more than doubled food intake in rats that were full already, suggesting that it was interfering with the rats' GLP-1 stop-eating signals.


In starving rats, the blocker had no effect, presumably because the hungry rats had no GLP-1 signal to be blocked.


Bloom said the researchers plan to study GLP-1's relationship to the recently discovered substance leptin, another signaler of satiety, which is created by fat cells and acts on the brain. One question is whether leptin does its job by turning on production of GLP-1 in the brain, Bloom said.


To turn the GLP-1 research into a pill for people, scientists might look for a substance that acts like GLP-1 but can reach the brain after being taken by mouth, he said.


Another possibility would be to devise a drug that slows the natural breakdown of GLP-1 so that it acts longer than normal, he said. That drug would be effective only if a person already is full and so has the GLP-1 signal.


Such a drug might make fat people eat less but not help anorexics starve themselves, he said.


Timothy Moran of Johns Hopkins University in Baltimore, who studies the body's regulation of appetite, said Bloom's study contains convincing evidence that GLP-1 plays a role in controlling food intake.


Such studies in rats have generally been shown to apply to people, he said.


At least four other kinds of peptides -- substances built up from amino acids -- also serve as the body's appetite-suppressing signals, he said.


As with these other peptides, it's too soon to tell whether the GLP-1 research can lead to a useful weight-loss drug, he said.