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

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Science  30 Jun 2000:
Vol. 288, Issue 5475, pp. 2379-2381
DOI: 10.1126/science.288.5475.2379

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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.

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