RRC ID 43149
Author Sugimoto Y, Naniwa Y, Nakamura T, Kato H, Yamamoto M, Tanabe H, Inoue K, Imaizumi A.
Title A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes.
Journal Arch Biochem Biophys
Abstract To identify the novel inhibitor of de novo lipogenesis in hepatocytes, we screened for inhibitory activity of triglyceride (TG) synthesis using [14C]acetate in the human hepatoma cell line, HepG2. Using this assay system we discovered the novel compound, benzofuranyl alpha-pyrone (TEI-B00422). TEI-B00422 also inhibited the incorporation of acetate into the triglyceride (TG) fraction in rat primary hepatocytes. In HepG2 cells, the incorporation of oleate into TG was unaffected. TEI-B00422 inhibited rat hepatic acetyl-CoA carboxylase (ACC), K(i)=3.3 microM, in a competitive manner with respect to acety-CoA but not fatty acid synthase and acyl-CoA transferase/diacylglycerol. Thus, these results suggest that the inhibition of TG synthesis by TEI-B00422 is based on the inhibitory action of ACC. The structure of TEI-B00422 is totally different from the known inhibitors of ACC and may be useful in the development of therapeutic agents to combat a number of metabolic disorders.
Volume 468(1)
Pages 44-8
Published 2007-12-1
DOI 10.1016/j.abb.2007.09.012
PII S0003-9861(07)00470-5
PMID 17950240
MeSH Acetyl Coenzyme A / antagonists & inhibitors* Acetyl Coenzyme A / metabolism* Animals Benzofurans / administration & dosage* Cell Line Enzyme Inhibitors / administration & dosage Fatty Acids / metabolism* Hepatoblastoma / metabolism* Hepatocytes / drug effects Hepatocytes / metabolism* Humans Liver Neoplasms / metabolism* Pyrones / administration & dosage* Rats
IF 3.391
Times Cited 15
Human and Animal Cells