Scientists look at ways to suppress appetite

For many researchers, the key to fighting obesity lies in understanding how the brain creates signals that tell us when to eat. After all, scientists know that brain cells, or neurons, send signals when our bodies need food and when we have eaten enough.

Studies in recent years have focused largely on receptors in the brain, such as leptin and serotonin, that alter signals in ways that can suppress our appetite for food.

But instead of looking at receptors, a group of scientists at Johns Hopkins School of Medicine has focused on finding chemical compounds that will make enzymes in the brain suppress appetites and burn body fat.

Dr. Gabriele Ronnett, a neuroscientist, was part of a team of researchers who discovered two years ago that injecting mice with a new compound stimulated a brain enzyme, known as CPT1, that prompted the mice to burn fat more quickly. They found that mice treated with the compound lost 50% more weight than a control group.

Earlier research had shown that the same compound, known as C75, shuts off another enzyme that plays a key role in food metabolism, cutting back on appetite. That enzyme, fatty acid synthase, or FAS for short, fires off neurons that send signals throughout the brain that make us feel hungry. By inhibiting fatty acid synthase, the compound essentially fools the brain into thinking the body no longer needs food.

Researchers at Johns Hopkins have narrowed their search from 400 potential compounds to a group of six they say could prove effective as weapons to combat obesity.

The researchers say Food and Drug Administration approval of a drug for either cancer or obesity is years away. But a pill that safely and effectively burns away fat or curbs appetites would have far-reaching health benefits -- and reap huge profits.

“Obesity is such a horrendous health problem it needs to be addressed on several fronts,” Ronnett said.

“If it’s not going to be a magic pill, I think what we have will be a good start.”

The Centers for Disease Control and Prevention announced recently that the number of U.S. deaths linked to poor diet and lack of exercise rose by 100,000 to 400,000 in 2000. The numbers make obesity a leading contributor to premature deaths among Americans, second only to tobacco.

Almost 130 million Americans, or 64%, are overweight, according to government calculations, an increase from 47% in 1980.

Moreover, a third of the U.S. population is obese, a category that means having a body mass index -- a calculation of weight and height -- that is 20% above recommended levels.

Some experts say responsibility for the nation’s weight problem lies with a culture focused so much around food consumption.

“Food is one of the few things you can reward yourself with almost anywhere, anytime,” said Allen Levine, a neuroscientist at the University of Minnesota. “You can eat a doughnut at your desk, but you can’t have sex in your office, or drink in public. Food is just so freely available.”

Levine has experimented with rats to try to understand the parts of our brain that create cravings for sweets. He has worked with a group of neurotransmitters, known as endo-genous opioids, that he and others think trigger the pleasure responses created by sweets.

His work has convinced him that cravings depend on individual circumstances.

“Rats will work harder for something with a sweet taste than something that tastes bland. But what you like is a flexible thing,” he said. “If you’re starving, even oatmeal tastes great.”

In Ronnett’s lab, it’s easy to see the difference between mice that are fed to become obese and mice on regular diets. After two months of feeding, the obese mouse is about twice the size of one with a regular appetite.

But there is a limit to the eating habits of even these mice.

“We don’t fatten them up too much,” she said. “That would be inhumane.”