Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors

With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have iden tified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid syn thase (FAS) inhibitors (cerulenin and a synthetic compound C75) Led to inhi bition of feeding and dramatic weight Loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin- independent manner that appears to be mediated by malonyl-coenzyme A. Thus, FAS may represent an important Link in feeding regulation and may be a pot ential therapeutic target.