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Compound that switches off appetite in mice discovered by Hopkins scientists

Team finds a key pathway to appetite regulation

June 23, 2000 -- Johns Hopkins scientists have produced a compound capable of rapidly turning off appetite in mice and causing weight loss similar in many ways to that achieved by fasting. When injected, the substance, which is apparently non-toxic to the mice, wipes out the animals' interest in food within 20 minutes. The effect of the chemical called C75 wears off a few days after injections stop, the researchers say, and the mice resume normal feeding.

The report on the work appears today in the journal Science.

"We are not claiming to have found the fabled weight-loss drug," says pathologist/biochemist Frank Kuhajda, M.D., spokesperson and research team member. "What we have found, using C75, is a major pathway in the brain that the body uses naturally in regulating appetite at least in mice." A similar system is likely in humans, the researchers say, but whether C75 works the same way awaits further research.

What's unusual, they explain, is that the pathway exists in the brain at all. Scientists normally look for the cascade of reactions, used to synthesize molecules called fatty acids, in the body's fat or liver tissue. Yet not only is the pathway found in certain brain cells, but these cells are concentrated in areas known to control appetite.

"It's unlikely that C75 ties directly into the wasting that occurs with cancer or infectious diseases," says biochemist Thomas M. Loftus, Ph.D., a team member. The scientists have also discounted direct links to leptins appetite-affecting substances produced by fat tissue whose discovery a few years ago sparked headlines and as-yet unrealized hopes for the perfect diet drug.

In support of their characterization of C75, the investigators note it caused a dramatic weight drop in leptin-free mice predisposed to obesity. Yet the compound also reversed the insulin-resistant form of diabetes those mice experience. It
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Contact: Marjorie Centofanti
mcentofanti@jhmi.edu
410-955-8725
Johns Hopkins Medical Institutions
29-Jun-2000


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