Lean mice adjust to appetite suppressant quickly, fat mice don't

Expanding their studies of an experimental compound that causes dramatic weight loss and appetite suppression in mice, Johns Hopkins researchers now report that lean mice rapidly adjust to daily doses of the drug and get their appetites back, while their obese counterparts do not.

Reporting in the Feb. 19 issue of the Proceedings of the National Academy of Sciences, the scientists show that the compound, called C75, kills the appetites of lean mice only the first day it's given. Mice engineered to be obese failed to start eating normally during the entire five days of the study, says Daniel Lane, Ph.D.

"The results suggest that being at a normal weight gives mice the ability to become quickly insensitive to the compound; that normal lean mice couldn't starve even when given C75 daily," says Lane, professor of biological chemistry in the school of medicine's Institute for Basic Biomedical Sciences. "We need to continue the experiment longer to see if obese mice develop insensitivity to the compound as they approach a normal weight, but so far it's very encouraging. We are closing in on a powerful biological signal in weight control."

C75, Lane says, blocks the action of the key machine for storing energy, an enzyme called fatty acid synthase, that is found in fat-producing tissues and in the brain, where it seems to be part of an appetite-sensing system. Building on his team's recent report that C75 alters levels of brain messengers that regulate appetite, the scientists set out to see how the compound worked over a period of five days.

"At the high doses we used for earlier, one-day studies, the lean mice didn't eat at all," says Lane. "We knew they wouldn't be able to survive not eating over the course of four or five days, so we used a lower dose that limited their eating to about half of normal."

Surprisingly, the scientists' concern was unnecessary, as the lean mice resumed normal eating habits after the fi

Contact: Joanna Downer
Johns Hopkins Medical Institutions

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