The Pharmaceutical Journal
Vol 268 No 7187 p274-79
2 March 2002

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Proceedings of the National Academy of Sciences (USA) (www.pnas.org)

Response to appetite suppressant differs between lean and obese mice

An appetite suppressant under investigation produces different responses in mice depending on whether they are lean or obese.

The appetite suppressant C75 is a potent inhibitor of fatty acid synthase that acts centrally and has been shown to reduce food intake and body weight in mice. However, researchers from the Johns Hopkins University School of Medicine, Baltimore, United States, have found that lean mice respond quicker than obese mice to C75, but then regain their appetites more quickly when given repeated doses.

The researchers say that C75 suppressed food intake by approximately 50 per cent in lean mice and by 95 per cent in obese mice during the first day of treatment. However, lean mice became tolerant to C75 over the following two to five days of treatment with food intake returning to near normal and rebound overeating occurring on cessation of treatment. During the same time period, food intake was suppressed by greater than 90 per cent in obese mice with an overall weight loss of 15.4 per cent and signs of incipient tolerance on day four (Proceedings of the National Academy of Sciences 2002;99:1921).

Professor Daniel Lane from the Johns Hopkins University School of Medicine, who was involved in the study, said: "The results suggest that being at normal weight gives mice the ability to become quickly insensitive to the compound." He added: "Normal lean mice could not starve even when given C75 daily."