Development of a ligand screening tool using full-length human peroxisome proliferator-activated receptor-expressing cell lines to ameliorate metabolic syndrome

Keisuke Tachibana, Kenji Ishimoto, Rika Takahashi, Hirokazu Kadono, Takuya Awaji, Tomohiro Yuzuriha, Toshiya Tanaka, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Shunji Aoki, Takefumi Doi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and include three subtypes (PPARα, PPARδ, and PPARγ). They regulate gene expression in a ligand-dependent manner. PPARα plays an important role in lipid metabolism. PPARγ is involved in glucose metabolism and is a potential therapeutic target in Type 2 diabetes. PPARδ ligands are candidates for the treatment of metabolic disorders. Thus, the detection of PPAR ligands may facilitate the treatment of various diseases. In this study, to identify PPAR ligands, we engineered reporter cell lines that can be used to quantify PPARγ and PPARδ activity. We evaluated several known ligands using these reporter cell lines and confirmed that they are useful for PPAR ligand detection. Furthermore, we evaluated extracts of approximately 200 natural resources and found various extracts that enhance reporter gene activity. Finally, we identified a main alkaloid of the Evodia fruit, evodiamine, as a PPARγ activator using this screening tool. These results suggest that the established reporter cell lines may serve as a useful cell-based screening tool for finding PPAR ligands to ameliorate metabolic syndromes.

Original languageEnglish
Pages (from-to)199-202
Number of pages4
JournalChemical and Pharmaceutical Bulletin
Volume67
Issue number3
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Ligand
  • Natural resource
  • Nuclear receptor
  • Peroxisome proliferator-activated receptor
  • Screening system
  • Tet-off system

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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