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Regulation of glucose and lipid metabolism through specific receptor-responsive FGF19 protein

Research Project

Project/Area Number 24659064
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionNational Fisheries University (2013)
Tohoku University (2012)

Principal Investigator

MIYATA Masaaki  独立行政法人水産大学校, その他部局等, 教授 (90239418)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsFGF19 / 脂肪性肝疾患 / 脂質代謝 / 細胞増殖 / FGF19受容体 / FGF受容体 / 細胞増殖作用 / 糖代謝 / FXR欠損マウス
Research Abstract

We tried to prepare mutant FGF19 protein (FGF19-7) that lacks the activity of cell proliferation. FGF19-7 treatment slightly decreased CYP7A1 mRNA levels in HepG2 cells. Treatment of mice with FGF19-7 did not stimulate the number of Ki-67 positive cells that is a marker of cell proliferation. Mice were fed a methionin- and choline- deficient (MCD) diet for 6 weeks and co-treated with FGF19 or FGF19-7 (40 nmol/kg) for 4 days. Serum ALT and hepatic triglyceride and free fatty acid levels were markedly increased in mice fed MCD diet. These levels were significantly decreased in the mice co-treated with FGF19 or FGF19-7 to a similar extent. These results suggest that treatment with FGF19-7 lacking the activity of cell proliferation protects against MCD diet-induced steatohepatitis.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (20 results)

All 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 2 results) Presentation (14 results) (of which Invited: 1 results)

  • [Journal Article] SREBP-2 negatively regulates FXR-dependent transcription of FGF19 in human intestinal cells2014

    • Author(s)
      M. Miyata, T. Hata, Y. Yamazoe and K. Yoshinari
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 443 Pages: 477-482

    • Related Report
      2013 Final Research Report
  • [Journal Article] SREBP-2 negatively regulates FXR-dependent transcription of FGF19 in human intestinal cells.2014

    • Author(s)
      M. Miyata, T. Hata, Y. Yamazoe and K. Yoshinari
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 443 Issue: 2 Pages: 477-482

    • DOI

      10.1016/j.bbrc.2013.11.126

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ileal apical sodium-dependent bile acid transporter protein levels are down-regulated through ubiquitin-dependent protein degradation induced by bile acids2013

    • Author(s)
      M. Miyata, H. Yamakawa, K. Hayashi, H. Kuribayashi, Y. Yamazoe and K. Yoshinari
    • Journal Title

      Euro. J. Pharmacol.

      Volume: 714 Issue: 1-3 Pages: 507-514

    • DOI

      10.1016/j.ejphar.2013.06.036

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enterobacteria-mediated deconjugation of taurocholic acid enhances ileal FXR signaling2012

    • Author(s)
      H. Kuribayashi, M. Miyata, H. Yamakawa, K. Yoshinari and Y. Yamazoe
    • Journal Title

      Eur. J. Pharmacol

      Volume: 697 Issue: 1-3 Pages: 132-138

    • DOI

      10.1016/j.ejphar.2012.09.048

    • Related Report
      2013 Final Research Report
  • [Journal Article] Involvement of multiple elements in FXR-mediatedtranscriptional activation of FGF192012

    • Author(s)
      M. Miyata, T. Hata, H. Yamakawa, T. Kagawa, K. Yoshinari and Y. Yamazoe
    • Journal Title

      J. Steroid Biochem. Mol. Biol.

      Volume: 132 Issue: 1-2 Pages: 41-47

    • DOI

      10.1016/j.jsbmb.2012.04.008

    • Related Report
      2013 Final Research Report
  • [Journal Article] 胆汁酸―FGF系による脂質代謝調節への腸管からのシグナル2012

    • Author(s)
      宮田昌明、山添 康
    • Journal Title

      The Lipid

      Volume: 23 Pages: 266-271

    • URL

      http://med.m-review.co.jp/magazine/detaill/J07_23_3_46-51.html

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] SREBP-2はヒト消化管由来細胞でFGF19のFXR依存的な転写を負に調節する2014

    • Author(s)
      宮田昌明、畑竜也、山添康、吉成浩一
    • Organizer
      日本農芸化学会2014年会
    • Place of Presentation
      東京
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] SREBP-2はヒト消化管由来細胞でFGF19のFXR依存的な転写を負に調節する2014

    • Author(s)
      宮田昌明、畑竜也、山添康、吉成浩一
    • Organizer
      日本農芸化学会 2014年会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] FGF19は非アルコール性脂肪性肝疾患モデルFxr欠損マウスの病態を改善する2013

    • Author(s)
      宮田 昌明, 松澤 瞳, 境田 裕美, 山添 康, 吉成 浩一
    • Organizer
      2013環境トキシコロジーフォーラム
    • Place of Presentation
      福岡
    • Year and Date
      2013-09-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸内細菌による胆汁酸代謝変換は回腸の胆汁酸吸収輸送担体の発現を制御する2013

    • Author(s)
      宮田昌明、山川泰輝、林謙次郎、吉成浩一、山添康
    • Organizer
      2013年度日本農芸化学会合同広島大会
    • Place of Presentation
      広島
    • Year and Date
      2013-09-06
    • Related Report
      2013 Final Research Report
  • [Presentation] LS174T細胞のFXRシグナルは活性型SREBP2により抑制的に調節される2013

    • Author(s)
      宮田昌明、畑竜也、山添康、吉成浩一
    • Organizer
      日本薬学会第133回年会
    • Year and Date
      2013-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 消化管FGF15/19シグナルによる肝機能の調節薬物代謝・分子毒性学2013

    • Author(s)
      宮田昌明
    • Organizer
      仙台セミナーー基礎研究から創薬・臨床へー
    • Place of Presentation
      仙台
    • Year and Date
      2013-02-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸内細菌による胆汁酸代謝変換は回腸の胆汁酸吸収輸送担体の発現を制御する2013

    • Author(s)
      宮田昌明、山川泰輝、林 謙次郎、吉成浩一、山添 康
    • Organizer
      2013年度 日本農芸化学会 合同広島大会
    • Place of Presentation
      広島
    • Related Report
      2013 Annual Research Report
  • [Presentation] FGF19は非アルコール性脂肪性肝疾患モデルFxr欠損 マウスの病態を改善する2013

    • Author(s)
      宮田 昌明,松澤 瞳,境田 裕美,山添 康,吉成 浩一
    • Organizer
      2013 環境トキシコロジーフォーラム
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] 回腸胆汁酸トランスポーターASBTの発現は腸内細菌代謝型胆汁酸シグナルに依存したユビキチン/タンパク質分解系で負に調節される2012

    • Author(s)
      宮田昌明、山川泰輝、林謙次郎、山添康
    • Organizer
      第34回胆汁酸研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-12-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸内細菌による胆汁酸の代謝変換がユビキチン/ライソゾーム分解系を介する回腸Asbtの抑制的な発現調節に関与する2012

    • Author(s)
      宮田昌明、山川泰輝、林謙次郎、吉成浩一、山添康
    • Organizer
      第27回日本薬物動態学会
    • Place of Presentation
      東京
    • Year and Date
      2012-11-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Antibacterial drug treatment causes enhanced levels of hepatic bile acid through alteration of ileal bile acid transporter expression2012

    • Author(s)
      M. Miyata, H. Yamakawa, Y. Yamazoe
    • Organizer
      The 6^<th> International Congress of Asian Society of Toxicology
    • Place of Presentation
      Sendai, Japan
    • Year and Date
      2012-07-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗菌薬投与による肝内胆汁酸レベルの上昇の機序―回腸胆汁酸吸収トランスポーター発現の解析2012

    • Author(s)
      宮田昌明、山川泰輝、山添康
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝胆汁酸合成の抑制に関与するマウス回腸FGF15発現の新規調節機序2012

    • Author(s)
      栗林 秀明、宮田昌明、山川泰輝、吉成浩一、山添 康
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 消化管FGF15/19シグナルによる肝機能の調節

    • Author(s)
      宮田昌明
    • Organizer
      薬物代謝・分子毒性学仙台セミナーー基礎研究から創薬・臨床へー
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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