With obesity affecting an ever-increasing proportion of society, the search for fat-fighting drugs seems to have a heightened sense of urgency. Now a report published today in the Proceedings of the National Academy of Sciences provides interesting insight into one potential weight-control drug that affects obese mice differently than it does normal animals.

Daniel Lane of Johns Hopkins University School of Medicine and his colleagues worked with a compound called C75, which had previously been shown to suppress appetite and cause dramatic weight loss in mice after one injection by inhibiting the enzyme fatty acid synthase (FAS). Building on findings that showed C75 alters levels of brain messengers that regulate appetite, the team investigated how mice responded to the compound over a five-day period. They found that C75 suppressed the appetite of both lean and obese mice on the first day it was administered. In subsequent days, however, the two types of mice showed dramatically different responses to the molecule. Whereas obese mice ate 90 percent less than their normal food intake for the entire five-day period, the lean mice returned to their regular eating patterns on the second day. "The results, Lane says, "suggest that being at a normal weight gives mice the ability to become quickly insensitive to the compound."

Moreover, when compared with mice eating the same number of calories, C75-treated animals lost more weight. Because animals must burn more calories than they consume in order to lose weight, the researchers propose that C75 might also increase energy expenditure of the mice, in addition to controlling their appetites. Though the implications for humans are still unclear, Lane suggests that scientists "are closing in on a powerful biological signal in weight control."