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Clue to Controlling Appetite Found

Discovery could one day lead to weight-loss pill in humans

MONDAY, Feb. 21, 2005 (HealthDayNews) -- For folks who have long wished that losing weight was just a matter of popping a pill, Johns Hopkins scientists report they are one step closer to finding a way to control appetite.

Injecting an enzyme that blocks fatty acid synthase (FAS) into the brains of mice acts on certain brain chemicals and results in decreased appetite, thereby reducing body weight, they report.

"We have been working on this control of food intake," explained lead researcher M. Daniel Lane, a distinguished service professor in the Department of Biological Chemistry. "Five years ago, we found a compound that we call C75 blocks food intake."

It works like this, Lane said: C75 blocks FAS and, when FAS is blocked, the amount of another compound, called malonyl-CoA, increases. That rise in malonyl-CoA suppresses some of the brain chemicals that increase appetite, he explained. In addition, the amount of other chemicals that suppress appetite is also increased.

In this latest study, Lane and his colleagues found C75 works by blocking the production of a compound called ghrelin, an appetite stimulant. Ghrelin is produced in the brain and the stomach, Lane noted.

To test their theory, Lane's team injected ghrelin into the mice. As expected, the ghrelin injection reversed the effect of C75.

"This brings us closer to the site where C75 acts," Lane said. "Now, we have to find out how malonyl-CoA prevents the secretion of ghrelin."

Lane's latest findings appear in this week's issue of the Proceedings of the National Academy of Sciences.

C75 has not been tested in humans, Lane said. He believes, however, that C75 or a similar compound could be used to reduce appetite. "But that's way out in the future," he said.

"The tantalizing lure of a 'silver bullet' to prevent weight gain and treat obesity propagates irrepressible hope alike among the public at large and scientific researchers alike," said Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine. "To date, such hopes have consistently been dashed."

Katz added there are reasons to be cautious about any drug for weight control. "Weight gain occurs because of more calories in than out," he said. "The physiologic mechanisms that favor weight gain are diverse, redundant and profound. To turn them off is tantamount to shutting down much that is fundamental to human metabolism. Intuition suggests such an endeavor is fraught with hazard."

Perhaps a C75 derivative will one day be one of the weapons used to combat obesity and its consequences, Katz said. But there's "no need to hold our breath and wait," he added.

"We already own the solution to obesity: increase daily calorie output above daily calorie intake. There will likely never be a medication as supportive of overall good health as the combination of healthful, portion-controlled eating, and regular physical activity," Katz stressed.

More information

The U.S. Department of Agriculture can tell you more about healthful eating.

SOURCES: M. Daniel Lane, Ph.D., distinguished service professor, Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore; David L. Katz, M.D., M.P.H., director, Prevention Research Center, Yale University School of Medicine, New Haven, Conn.; Feb. 21-25, 2005, Proceedings of the National Academy of Sciences
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