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Study on the activity of nuclear receptor PPAR delta that regulates energy expenditure

Research Project

Project/Area Number 16K13044
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionOsaka University

Principal Investigator

Tachibana Keisuke  大阪大学, 薬学研究科, 講師 (30432446)

Co-Investigator(Kenkyū-buntansha) 樋野 展正  大阪大学, 薬学研究科, 助教 (90469916)
Research Collaborator Fukuda Syohei  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords生活習慣病 / 核内受容体 / PPARδ / 翻訳後修飾 / 光クロスリンク / リガンドスクリーニング / 核内受容体PPARδ / PPAR
Outline of Final Research Achievements

Peroxisome proliferator-activated receptor delta (PPARδ) belongs to the nuclear hormone receptor superfamily. PPARδ regulates gene expression in fatty acid oxidation and energy expenditure. In this study, we constructed a skeletal muscle differentiation system using cultured cells for in vitro analysis of the function of PPARδ in human skeletal muscle. We also engineered reporter cell lines that can be used to quantify PPARδ activity. We then evaluated extracts of natural resources and found various extracts that enhance reporter gene activity. Furthermore, we searched for factors that interact with PPARδ. The results of these studies will help to elucidate the regulatory mechanism of energy consumption through PPARδ.

Academic Significance and Societal Importance of the Research Achievements

本研究では、近年問題となっている肥満・生活習慣病の克服に向けて、骨格筋でエネルギー消費に寄与する核内受容体PPARδの活性制御に関する知見を得た。PPARの機能については、げっ歯類とヒトとの間で種差のあることが知られている。構築したヒト培養細胞を用いた骨格筋分化系は、ヒトでの機能を解析する上で優れたツールになりうる。また、明らかにしたPPARδの翻訳後修飾と活性との関連については、これまでにない翻訳後修飾を介した活性制御機構の開発に繋がり意義深い。さらに、同定したPPARδを活性化する天然物抽出エキスやその成分を用いることで、エネルギー消費可能な医薬品等の開発に繋がることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2016 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Development of a Ligand Screening Tool Using Full-Length Human Peroxisome Proliferator-Activated Receptor-Expressing Cell Lines to Ameliorate Metabolic Syndrome2019

    • Author(s)
      Tachibana Keisuke、Ishimoto Kenji、Takahashi Rika、Kadono Hirokazu、Awaji Takuya、Yuzuriha Tomohiro、Tanaka Toshiya、Hamakubo Takao、Sakai Juro、Kodama Tatsuhiko、Aoki Shunji、Doi Takefumi
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 3 Pages: 199-202

    • DOI

      10.1248/cpb.c18-00627

    • NAID

      130007605823

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-03-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of peroxisome proliferator?activated receptor α (PPARα) activators with a ligand-screening system using a human PPARα-expressing cell line2018

    • Author(s)
      Tachibana Keisuke、Yuzuriha Tomohiro、Tabata Ryotaro、Fukuda Syohei、Maegawa Takashi、Takahashi Rika、Tanimoto Keiichi、Tsujino Hirofumi、Nunomura Kazuto、Lin Bangzhong、Matsuura Yoshiharu、Tanaka Toshiya、Hamakubo Takao、Sakai Juro、Kodama Tatsuhiko、Kobayashi Tadayuki、Ishimoto Kenji、Miyachi Hiroyuki、Doi Takefumi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 26 Pages: 10333-10343

    • DOI

      10.1074/jbc.ra118.002077

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development Of Novel Non-fibrate Peroxisome Proliferator-activated Receptor Ligand For Treating Nonalcoholic Steatohepatitis2018

    • Author(s)
      Keisuke TACHIBANA, Tomohiro YUZURIHA, Ryotaro TABATA, Syohei FUKUDA, Kazuto NUNOMURA, Bangzhong LIN, Tadayuki KOBAYASHI, Masuo KONDOH, Kenji ISHIMOTO, Hiroyuki MIYACHI, Takefumi DOI
    • Organizer
      CRS Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development Of Novel Non-fibrate Peroxisome Proliferator-activated Receptor Ligand For Treating Nonalcoholic Steatohepatitis2018

    • Author(s)
      Keisuke Tachibana, Tomohiro Yuzuriha, Ryotaro Tabata, Syohei Fukuda, Kazuto Nunomura, Bangzhong Lin, Tadayuki Kobayashi, Masuo Kondoh, Kenji Ishimoto, Hiroyuki Miyachi, Takefumi Doi
    • Organizer
      the 2018 Controlled Release Society Annual Meeting(発表確定済)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] DMDモデル細胞の構築とSSOの活性評価2016

    • Author(s)
      下剛典, 細木華奈, 橘敬祐, 小比賀聡, 横田俊文
    • Organizer
      日本核酸医薬学会 第2回年会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report
  • [Remarks] 大阪大学大学院薬学研究科生命情報解析学分野ホームページ

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b018/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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