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Science 30 June 2000:
Vol. 288. no. 5475, pp. 2379 - 2381
DOI: 10.1126/science.288.5475.2379
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Reports

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

Thomas M. Loftus, 1 Donna E. Jaworsky, 2 Gojeb L. Frehywot, 4 Craig A. Townsend, 4 Gabriele V. Ronnett, 2 M. Daniel Lane, 1 Francis P. Kuhajda 3*

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.

1 Department of Biological Chemistry,
2 Department of Neuroscience,
3 Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4 Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
*   To whom correspondence should be addressed. E-mail: fkuhajda{at}jhmi.edu

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