| 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
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
