Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors.
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.
Loftus
T M
TM
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jaworsky
D E
DE
Frehywot
G L
GL
Townsend
C A
CA
Ronnett
G V
GV
Lane
M D
MD
Kuhajda
F P
FP
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001067:Appetite Depressants / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002569:Cerulenin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D005215:Fasting; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects*
D001067:Appetite Depressants; D004791:Enzyme Inhibitors; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D002569:Cerulenin; D008316:Malonyl Coenzyme A; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase