Document Detail


Anti-obesity activity of a novel lipid synthesis inhibitor.
MedLine Citation:
PMID:  6534895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A novel anti-obesity agent which inhibits fatty acid synthesis and stimulates fatty acid oxidation is described. The hydrochloride salt of Ro 22-0654 (4-amino-5-ethyl-3-thiophenecarboxylic acid methyl ester) is a potent inhibitor of fatty acid and cholesterol synthesis in rat-isolated hepatocytes. Hepatic fatty acid synthesis was inhibited in vivo in a dose-dependent fashion with a duration of action of approximately 8 h. Adipose tissue fatty acid synthesis was also inhibited in vivo. Inhibition of fatty acid synthesis occurs without any apparent effect on several lipogenic enzymes, the tricarboxylic acid cycle, and the pentose phosphate shunt. Ro 22-0654 also stimulated fatty acid oxidation (in vitro) and lipolysis (in vivo). In long-term studies (2 months), Ro 22-0654 decreased body weight gain in Sprague Dawley and genetically-obese Zucker rats. Food intake was decreased following a single dose and for several days during chronic treatment. However, while food intake quickly returned to normal, body weight gain remained lower in treated rats. The effect on body weight gain can be ascribed to decreased total body lipid content in the absence of an effect on lean body mass. It is suggested that Ro 22-0654 may have utility in the treatment of human obesity.
Authors:
J Triscari; A C Sullivan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of obesity     Volume:  8 Suppl 1     ISSN:  -     ISO Abbreviation:  Int J Obes     Publication Date:  1984  
Date Detail:
Created Date:  1985-07-08     Completed Date:  1985-07-08     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  7703240     Medline TA:  Int J Obes     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  227-39     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / drug effects,  metabolism*
Animals
Fatty Acids / biosynthesis
Female
Lipid Metabolism*
Lipids / biosynthesis
Lipolysis / drug effects
Liver Glycogen / biosynthesis
Obesity / drug therapy*,  metabolism
Oxidation-Reduction
Rats
Rats, Inbred Strains
Rats, Zucker
Thiophenes / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Lipids; 0/Liver Glycogen; 0/Thiophenes; 81741-99-3/Ro 22-0654

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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