A Small Molecule That Blocks Fat Synthesis By Inhibiting the Activation of SREBP

Shinji Kamisuki, Qian Mao, Lutfi Abu-Elheiga, Ziwei Gu, Akira Kugimiya, Youngjoo Kwon, Tokuyuki Shinohara, Yoshinori Kawazoe, Shin ichi Sato, Koko Asakura, Hea Young Park Choo, Juro Sakai, Salih J. Wakil, Motonari Uesugi

Research output: Contribution to journalArticlepeer-review

202 Citations (Scopus)


Sterol regulatory element binding proteins (SREBPs) are transcription factors that activate transcription of the genes involved in cholesterol and fatty acid biosynthesis. In the present study, we show that a small synthetic molecule we previously discovered to block adipogenesis is an inhibitor of the SREBP activation. The diarylthiazole derivative, now called fatostatin, impairs the activation process of SREBPs, thereby decreasing the transcription of lipogenic genes in cells. Our analysis suggests that fatostatin inhibits the ER-Golgi translocation of SREBPs through binding to their escort protein, the SREBP cleavage-activating protein (SCAP), at a distinct site from the sterol-binding domain. Fatostatin blocked increases in body weight, blood glucose, and hepatic fat accumulation in obese ob/ob mice, even under uncontrolled food intake. Fatostatin may serve as a tool for gaining further insights into the regulation of SREBP.

Original languageEnglish
Pages (from-to)882-892
Number of pages11
JournalChemistry and Biology
Issue number8
Publication statusPublished - 2009 Aug 28




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