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

Tadashi Mori, Masafumi Hidaka, Hiroko Ikuji, Ibuki Yoshizawa, Haruhiko Toyohara, Toru Okuda, Chiyoko Uchida, Tomoichiro Asano, Mari Yotsu-Yamashita, Takafumi Uchida

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)832-838
    Number of pages7
    JournalBioscience, Biotechnology and Biochemistry
    Volume78
    Issue number5
    DOIs
    Publication statusPublished - 2014

    Keywords

    • Adipose cell
    • High-throughput screen
    • Obesity
    • Prolyl isomerase
    • Seaweed polyphenol

    ASJC Scopus subject areas

    • Biotechnology
    • Analytical Chemistry
    • Biochemistry
    • Applied Microbiology and Biotechnology
    • Molecular Biology
    • Organic Chemistry

    Fingerprint

    Dive into the research topics of 'A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation'. Together they form a unique fingerprint.

    Cite this