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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
Read the Full Text
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- F. Diraison, E. Dusserre, H. Vidal, M. Sothier, and M. Beylot (2002)
Am J Physiol Endocrinol Metab
282, E46-E51
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- Effect of a fatty acid synthase inhibitor on food intake and expression of hypothalamic neuropeptides.
- T. Shimokawa, M. V. Kumar, and M. D. Lane (2001)
PNAS
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- Construction and Analysis of Mouse Strains Lacking the Ubiquitin Ligase UBR1 (E3alpha ) of the N-End Rule Pathway.
- Y. T. Kwon, Z. Xia, I. V. Davydov, S. H. Lecker, and A. Varshavsky (2001)
Mol. Cell. Biol.
21, 8007-8021
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- Peripheral Signals Conveying Metabolic Information to the Brain: Short-Term and Long-Term Regulation of Food Intake and Energy Homeostasis.
- P. J. Havel (2001)
Experimental Biology and Medicine
226, 963-977
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- Brain glucose-sensing mechanisms: ubiquitous silencing by aglycemia vs. hypothalamic neuroendocrine responses.
- C. V. Mobbs, L.-M. Kow, and X.-J. Yang (2001)
Am J Physiol Endocrinol Metab
281, E649-E654
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- Response of Bacillus subtilis to Cerulenin and Acquisition of Resistance.
- G. E. Schujman, K.-H. Choi, S. Altabe, C. O. Rock, and D. de Mendoza (2001)
J. Bacteriol.
183, 3032-3040
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