Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors

Science. 2000 Jun 30;288(5475):2379-81. doi: 10.1126/science.288.5475.2379.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyl-CoA Carboxylase / antagonists & inhibitors
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Appetite / drug effects*
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / chemical synthesis
  • Appetite Depressants / pharmacology*
  • Cerulenin / pharmacology
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Fasting
  • Fatty Acid Synthases / antagonists & inhibitors*
  • Fatty Acid Synthases / metabolism
  • Female
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Injections, Intraventricular
  • Leptin / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Malonyl Coenzyme A / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuropeptide Y / administration & dosage
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism
  • Neuropeptide Y / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Weight Loss / drug effects*

Substances

  • Appetite Depressants
  • Enzyme Inhibitors
  • Leptin
  • Neuropeptide Y
  • RNA, Messenger
  • Cerulenin
  • Malonyl Coenzyme A
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase