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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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Appetite Suppression and Weight Reduction by a Centrally Active Aminosterol.
R. S. Ahima, H. R. Patel, N. Takahashi, Y. Qi, S. M. Hileman, and M. A. Zasloff (2002)
Diabetes 51, 2099-2104
   Abstract »    Full Text »    PDF »
Hydroxycitrate Has Long-Term Effects on Feeding Behavior, Body Weight Regain and Metabolism after Body Weight Loss in Male Rats.
M. Leonhardt and W. Langhans (2002)
J. Nutr. 132, 1977-1982
   Abstract »    Full Text »    PDF »
A Biotin Analog Inhibits Acetyl-CoA Carboxylase Activity and Adipogenesis.
K. L. Levert, G. L. Waldrop, and J. M. Stephens (2002)
J. Biol. Chem. 277, 16347-16350
   Abstract »    Full Text »    PDF »
A Missense Mutation in the fabB ({beta}-Ketoacyl-Acyl Carrier Protein Synthase I) Gene Confers Thiolactomycin Resistance to Escherichia coli.
S. Jackowski, Y.-M. Zhang, A. C. Price, S. W. White, and C. O. Rock (2002)
Antimicrob. Agents Chemother. 46, 1246-1252
   Abstract »    Full Text »    PDF »
A Y2 Receptor Mimetic Aptamer Directed against Neuropeptide Y.
D. Proske, M. Hofliger, R. M. Soll, A. G. Beck-Sickinger, and M. Famulok (2002)
J. Biol. Chem. 277, 11416-11422
   Abstract »    Full Text »    PDF »
Differential effects of a centrally acting fatty acid synthase inhibitor in lean and obese mice.
M. V. Kumar, T. Shimokawa, T. R. Nagy, and M. D. Lane (2002)
PNAS 99, 1921-1925
   Abstract »    Full Text »    PDF »
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake.
S. Obici, Z. Feng, K. Morgan, D. Stein, G. Karkanias, and L. Rossetti (2002)
Diabetes 51, 271-275
   Abstract »    Full Text »    PDF »
Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity.
F. Diraison, E. Dusserre, H. Vidal, M. Sothier, and M. Beylot (2002)
Am J Physiol Endocrinol Metab 282, E46-E51
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »
Cerulenin Mimics Effects of Leptin on Metabolic Rate, Food Intake, and Body Weight Independent of the Melanocortin System, but Unlike Leptin, Cerulenin Fails to Block Neuroendocrine Effects of Fasting.
H. Makimura, T. M. Mizuno, X.-J. Yang, J. Silverstein, J. Beasley, and C. V. Mobbs (2001)
Diabetes 50, 733-739
   Abstract »    Full Text »


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