A small molecule that blocks fat synthesis by inhibiting the activation of SREBP.

Abstract	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.
Authors	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
Journal	Chemistry & biology (Chem Biol) Vol. 16 Issue 8 Pg. 882-92 (Aug 28 2009) ISSN: 1879-1301 [Electronic] United States
PMID	19716478 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Blood Glucose Fatty Acids Intracellular Signaling Peptides and Proteins Membrane Proteins Pyridines SREBP cleavage-activating protein Sterol Regulatory Element Binding Proteins Thiazoles fatostatin
Topics	Animals Blood Glucose (metabolism) Body Weight CHO Cells Cricetinae Cricetulus Fatty Acids (biosynthesis, metabolism) Humans Intracellular Signaling Peptides and Proteins (metabolism) Membrane Proteins (metabolism) Mice Mice, Obese Protein Binding Protein Structure, Tertiary Pyridines (chemistry, pharmacology) Sterol Regulatory Element Binding Proteins (antagonists & inhibitors, chemistry, metabolism) Thiazoles (chemistry, pharmacology) Transcription, Genetic

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