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
