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 journalArticle

14 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 Jan 1

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

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