A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation

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  • Tadashi Mori
    Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
  • Masafumi Hidaka
    Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
  • Hiroko Ikuji
    Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
  • Ibuki Yoshizawa
    Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
  • Haruhiko Toyohara
    Graduate School of Agriculture, Kyoto University, Kyoto, Japan
  • Toru Okuda
    Tamagawa University, Research Center, Tokyo, Japan
  • Chiyoko Uchida
    Department of Human Development and Culture, Fukushima University, Fukushima, Japan
  • Tomoichiro Asano
    Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Hiroshima, Japan
  • Mari Yotsu-Yamashita
    Bioorganic Chemistry of Natural Products, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
  • Takafumi Uchida
    Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan

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<jats:title>Abstract</jats:title> <jats:p>The peptidyl prolyl cis/trans isomerase Pin1 enhances the uptake of triglycerides and the differentiation of fibroblasts into adipose cells in response to insulin stimulation. Pin1 downregulation could be a potential approach to prevent and treat obesity-related disorders. In order to identify an inhibitor of Pin1 that exhibited minimal cytotoxicity, we established a high-throughput screen for Pin1 inhibitors and used this method to identify an inhibitor from 1,056 crude fractions of two natural product libraries. The candidate, a phlorotannin called 974-B, was isolated from the seaweed, Ecklonia kurome. 974-B inhibited the differentiation of mouse embryonic fibroblasts and 3T3-L1 cells into adipose cells without inducing cytotoxicity. We discovered the Pin1 inhibitor, 974-B, from the seaweed, E. kurome, and showed that it blocks the differentiation of fibroblasts into adipose cells, suggesting that 974-B could be a lead drug candidate for obesity-related disorders.</jats:p>

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