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

Kamisuki, Shinji, Mao, Qian, Abu-Elheiga, Lutfi, Gu, Ziwei, Kugimiya, Akira, Kwon, Youngjoo, Shinohara, Tokuyuki, Kawazoe, Yoshinori, Sato, Shin-ichi, Asakura, Koko, Choo, Hea-Young Park, Sakai, Juro, Wakil, Salih J., Uesugi, Motonari·2009·Chemistry & Biology
DOI 10.1016/j.chembiol.2009.07.007
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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.

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Crossref · 10.1016/j.chembiol.2009.07.007

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  • Alternative ways to reduce neuronal cholesterol such as inhibition of SREBP by fatostatin or induction of cholesterol export by LXR agonists T0901317 and 24-hydroxycholesterol also reduced pThr231Tau/tTau.

    “Alternative ways to reduce neuronal cholesterol such as inhibition of sterol regulatory element-binding protein (SREBP)-mediated transcriptional activation of cholesterol synthetic genes by fatostatin (Kamisuki et al., 2009) (Figures 2C, S2H, and S2I) or induction of cholesterol export by liver X receptor (LXR) agonists (Figure 2A) T0901317 and 24-hydroxycholesterol (Figures 2C, S2F, and S2G) also”

    From Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons (2019) · cites this paper as Kamisuki et al., 2009

Citations

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Research works printed but not linked: 31

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Metadata

Authors
Kamisuki, S., Mao, Q., Abu-Elheiga, L., Gu, Z., Kugimiya, A., Kwon, Y., Shinohara, T., Kawazoe, Y., Sato, S.-I., Asakura, K., Choo, H.-Y. P., Sakai, J., Wakil, S. J., & Uesugi, M.
Venue
Chemistry & Biology
Publisher
Elsevier BV
Published
2009-08
Volume
16
Issue
8
Pages
882-892
ISSN
1074-5521
DOI
10.1016/j.chembiol.2009.07.007
Cited by
269
References
3
Language
en
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