A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes.

A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes. Research Abstract Details 

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A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes. Abstract Text:

Yoshinori Sugimoto,Yoshimitsu Naniwa,Takayuki Nakamura,Hirotsugu Kato,Masanori Yamamoto,Hirofumi Tanabe,Kinji Inoue,Atsushi Imaizumi,Yoshinori Sugimoto,Yoshimitsu Naniwa,Takayuki Nakamura,Hirotsugu Kato,Masanori Yamamoto,Hirofumi Tanabe,Kinji Inoue,Atsushi Imaizumi,

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.

A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes. Publishing Authors By Initials

Y Sugimoto,Y Naniwa,T Nakamura,H Kato,M Yamamoto,H Tanabe,K Inoue,A Imaizumi,Y Sugimoto,Y Naniwa,T Nakamura,H Kato,M Yamamoto,H Tanabe,K Inoue,A Imaizumi,

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A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Archives of biochemistry and biophysics

VOLUME: 468

Page Numbers: 44-8

Journal Abbreviation: Arch. Biochem. Biophys.

ISSN: 1096-0384

DAY: 25

MONTH: 09

YEAR: 2007

A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes. Information

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LANGUAGE: eng

NlmUniqueID: 372430

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Grant and Affiliation Information for A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes.

AFFILIATION: Teijin Pharma Limited, Pharmaceutical Discovery Research Laboratories, Institute for Bio-medical Research, 4-3-2, Asahigaoka, Hino Tokyo 191-8512, Japan. y.sugimoto@teijin.co.jp

Country: United States

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MEDLINETA: Arch Biochem Biophys

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