Can't Stop Eating? Oh Rats!

Scientists have identified another substance in the brains of rats that suppresses appetite, a possible hint toward the development of a new anti-obesity pill.

The discovery sheds light on the mystery of how the previously known hormone leptin helps the brain control appetite.

It's too soon to tell whether the newly identified substance, called CART, will lead to a slim-down pill. But experts called the work a significant step toward understanding the brain's complex machinery for controlling appetite.

The work is presented in Thursday's issue of the journal Nature by researchers in Denmark, including Dr. Peter Kristensen of Novo Nordisk Inc., which makes pharmaceuticals.

A similar report, from Dr. Michael J. Kuhar and colleagues at Emory University's Yerkes Regional Primate Center in Atlanta, will appear in an upcoming issue of the journal Synapse.

CART joins a long list of substances in the body that are known to influence appetite. But Kuhar said he believes CART is pivotal in the brain's regulation of hunger.

CART stands for "cocaine- and amphetamine-regulated transcript." It got its name because it was first identified in rats that had been give those drugs, which stimulate production of CART. A protein virtually identical to rat CART has been found in humans, Kristensen said.

The Danish researchers reported that when they blocked the effect of CART in the brain, rats ate more than usual. That indicates that CART normally acts as a brake on appetite.

When scientists injected CART into the brains of rats, the animals ate less than usual. And CART injections blocked the effect of a powerful appetite stimulant called neuropeptide Y.

Other results suggest that leptin cuts appetite in part by turning on production of CART. Mice that couldn't make leptin because of genetic mutations made virtually no CART, but when the animals were injected with leptin, CART levels went up.

Previous studies had shown that leptin reduces the brain's production of neuropeptide Y. So the new work suggests that leptin basically pushes on an appetite brake and eases up on a gas pedal, by boosting levels of CART while reducing levels of neuropeptide Y.

"It's a very important piece of the puzzle because it helps to explain leptin's actions," said Bart Hoebel of Princeton University, who didn't participate in the new study.

If scientists can find drugs that will mimic CART's effects, it could lead to an appetite-reducing pill, Kristensen said.

Written by Malcolm Ritter