Reduced Food Intake and Body Weight in Mice Treated with Fatty Acid Synthase Inhibitors

TLDR

Obesity drives interest in mechanisms that control appetite and body weight. In mice, fatty acid synthase inhibitors such as cerulenin and C75 suppress feeding, cause dramatic weight loss, downregulate hypothalamic neuropeptide Y, and act via a leptin‑independent, malonyl‑CoA–mediated pathway, indicating FAS as a key regulator of appetite and a potential therapeutic target.

Abstract

With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) led to inhibition 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 potential therapeutic target.