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Role of endocrine FGF in digestion and metabolic regulation

Research Project

Project/Area Number 16K09800
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionNagoya City University (2017-2018)
Kyoto University (2016)

Principal Investigator

Tanaka Tomohiro  名古屋市立大学, 大学院医学研究科, 准教授 (20402894)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsFGF / 脂質代謝 / NASH / 膵液 / オミックス / 消化
Outline of Final Research Achievements

Among endocrine FGFs, we here studied the functional role of FGF19 in pancreatic exocrine function and in the pathogenesis of non-alcoholic steatohepatitis. By collecting pancreatic juice from rats, we discovered that FGF19 or FGF21 injection lead to increased rate of lipase secretion into pancreatic juice. To investigate whether FGF19 effects on pancreas is mediated by beta Klotho, a specific co-receptor of FGF19, we newly generated beta Klotho knockout rats by CRISPR/Cas9 system. Although we have established a knockout rat, we could not efficiently obtain sufficient numbers of homozygous knockout rats, making the pancreatic juice collection pending until enough numbers of rats are available. We performed hisologic as well as transcriptomic analysis of the liver in beta Klotho knockout mice and found that the mice are good model of non-alcoholic steatohepatitis in humans from the aspect of not only steatosis, but of inflammation and hepatocyte injury.

Academic Significance and Societal Importance of the Research Achievements

本研究により、脂質や脂溶性栄養素の消化と吸収、体内分配を統一的に制御するFGF19 - beta Klothoシステムの生理的、病態生理的意義が明らかとなった。これまで膵消化酵素の分泌を制御するホルモンとしては、セクレチンやコレシストキニンが知られていたが、本研究により回腸遠位から分泌される新しいホルモンFGF19が膵液量の増加を伴わずに膵消化酵素、特にリパーゼの分泌を促進することが明らかとなった。また近年、我が国においても有病率の増加が懸念されている非アルコール性脂肪性肝炎(NASH)の病態における胆汁酸・脂質代謝異常の実体が明らかとなった。

Report

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

    (27 results)

All 2018 2017 2016

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] An Autopsy Case of Pulmonary Tumor Thrombotic Microangiopathy Due to Rapidly Progressing Colon Cancer in a Patient with Type 2 Diabetes2018

    • Author(s)
      Ohguchi H, Imaeda K, Hotta A, Kakoi S, Yasuda S, Shimizu Y, Hayakawa A, Mishina H, Hasegawa C, Ito S, Ogawa K, Yagi T, Koyama H, Tanaka T, Kato H, Takahashi S, Joh T.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 17 Pages: 2533-2539

    • DOI

      10.2169/internalmedicine.0204-17

    • NAID

      130007479948

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-09-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats2018

    • Author(s)
      Izumi Ryota、Kusakabe Toru、Noguchi Michio、Iwakura Hiroshi、Tanaka Tomohiro、Miyazawa Takashi、Aotani Daisuke、Hosoda Kiminori、Kangawa Kenji、Nakao Kazuwa
    • Journal Title

      Journal of Lipid Research

      Volume: 59 Issue: 9 Pages: 1575-1585

    • DOI

      10.1194/jlr.m082099

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 健康長寿の基盤としてのホルモン-栄養素間相互作用の研究2018

    • Author(s)
      田中智洋
    • Journal Title

      平成29年度 井村臨床研究奨励賞受賞記念論文

      Volume: 73 Pages: 119-124

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Case of Euthyroid Graves’ Ophthalmopathy in a Patient Sero-Negative for TSH Receptor Autoantibody2018

    • Author(s)
      A. Hotta, T. Tanaka, H. Kato, S. Kakoi, Y. Shimizu, C. Hasegawa, A. Hayakawa, S. Yasuda, K. Ogawa, S. Ito, H. Ohguchi, T. Yagi, H. Koyama, M. Kawamura, K. Sugitani, Y. Ogura, T. Joh, and K. Imaeda. (Corresponding author)
    • Journal Title

      Case Rep Endocrinol,

      Volume: 1707959 Pages: 1-6

    • DOI

      10.1155/2018/1707959

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon promotes colon cancer cell growth via regulating AMPK and MAPK pathways2018

    • Author(s)
      Yagi Takashi、Kubota Eiji、Koyama Hiroyuki、Tanaka Tomohiro、Kataoka Hiromi、Imaeda Kenro、Joh Takashi
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 12 Pages: 10650-10664

    • DOI

      10.18632/oncotarget.24367

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Switching of other dipeptidyl peptidase 4 inhibitors to alogliptin improves glycemic control in Japanese patients with type2 diabetes mellitus.2018

    • Author(s)
      T. Yagi, T. Tanaka, Y. Hayashi, T. Mizuno, K. Ogawa, H. Koyama, K. Imaeda, T. Joh.
    • Journal Title

      Nagoya Medical Journal

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fgf21 regulates T-cell development in the neonatal and juvenile thymus.2017

    • Author(s)
      Nakayama Y, Masuda Y, Ohta H, Tanaka T, Washida M, Nabeshima YI, Miyake A, Itoh N, Konishi M
    • Journal Title

      Scientific Reports

      Volume: 23 Issue: 1 Pages: 330-330

    • DOI

      10.1038/s41598-017-00349-8

    • NAID

      120006305890

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suspected case of lipoedema in Japanese woman with a characteristic histology in skin biopsy2017

    • Author(s)
      H. Koyama, T. Tanaka, K. Imaeda.
    • Journal Title

      BMJ Case Rep

      Volume: 該当なし Pages: bcr-2017-221049

    • DOI

      10.1136/bcr-2017-221049

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reevaluation of anti-obesity action of mazindol and elucidation of its effect on the reward system2016

    • Author(s)
      D. Aotani, C.Son, Y. Shimizu, H. Nomura, T. Hikida, T. Kusakabe, T. Tanaka, T. Miyazawa, K. Hosoda,
    • Journal Title

      Neuroscience Letters

      Volume: 633 Pages: 141-145

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] アミノ酸恒常性における脂肪細胞のβ-Klothoの意義2018

    • Author(s)
      田中智洋、鍋島陽一
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肥満の報酬系異常におけるレプチンの意義2018

    • Author(s)
      青谷大介、野村英生、清水彬礼、孫徹、田中智洋、細田公則、中尾一和
    • Organizer
      第30回分子糖尿病学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ペムプロリズマブ投与後に甲状腺クリーゼを発症した1例2018

    • Author(s)
      伊藤峻介、青谷大介、清水優希、早川暁子、加藤春佳、栫昭太、長谷川千恵、堀田明沙美、小川健人、八木崇志、小山博之、田中智洋
    • Organizer
      第28回臨床内分泌代謝Update
    • Related Report
      2018 Annual Research Report
  • [Presentation] 著明な低アルブミン血症と糖尿病性ケトアシドーシスを合併した1型糖尿病の一例2018

    • Author(s)
      清水優希、小山博之、伊藤峻介、早川暁子、長谷川千恵、栫昭太、加藤春佳、堀田明沙美、八木崇志、青谷大介、田中智洋
    • Organizer
      第92回日本糖尿病学会中部地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大量のインスリン投与を要した肝性糖尿病にインスリン分泌促進剤が有効であった症例2018

    • Author(s)
      栫昭太、加藤春佳、清水優希、早川暁子、長谷川千恵、堀田明沙美、伊藤峻介、八木崇志、小山博之、青谷大介、田中智洋
    • Organizer
      第92回日本糖尿病学会中部地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フラッシュグルコースモニタリングが低血糖の発生に有用であった高齢糖尿病患者の1例2018

    • Author(s)
      八木崇志、早川暁子、長谷川千恵、清水優希、栫昭太、堀田明沙美、伊藤峻介、小山博之、青谷大介、田中智洋
    • Organizer
      第92回日本糖尿病学会中部地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高脂肪食を負荷したレプチン過剰発現マウスは早期にレプチン抵抗性を生じる2018

    • Author(s)
      青谷大介、野村英生、孫徹、田中智洋、細田公則、中尾一和
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 視床下部セリンプロテアーゼ阻害分子SerpinA3によるレプチン抵抗性の誘導2018

    • Author(s)
      金子賢太朗、雲財知、荻野陽平、Guo Tingting、園山拓洋、田中智洋、鍋島陽一、中尾一和
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 視床下部レプチン抵抗性関連分子SerpinA3の同定2018

    • Author(s)
      田中智洋、金子賢太朗、園山拓洋、雲財知、Guo Tingting、八木崇志、小山博之、青谷大介、中尾一和
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レプチン感受性における細胞内糖質コルチコイド活性調節の意義2018

    • Author(s)
      Guo Tingting、田中智洋、園山拓洋、金子賢太朗、荻野陽平、小川健人、八木崇志、小山博之、青谷大介、細井徹、小澤孝一郎、中尾一和
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂肪細胞のβKlothoによる血中アミノ酸恒常性の制御2017

    • Author(s)
      田中智洋、鍋島陽一
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新しい腸管ホルモンFGF19による胆汁酸とエネルギー代謝の制御2017

    • Author(s)
      田中智洋、小林加奈子、小山博之、今枝憲郎、中尾一和、鍋島陽一、城卓志
    • Organizer
      第14回日本消化管学会総会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 糖尿病患者の大腸癌リスク上昇における高グルカゴン血症の意義の検討2017

    • Author(s)
      八木崇志、田中智洋、田中智洋、小山博之、久保田英嗣、今枝憲郎
    • Organizer
      第29回分子糖尿病学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] グレリン分泌細胞におけるGPCR発現解析および新規調節因子の探索2016

    • Author(s)
      小山博之、岩倉 浩、坂東美佳、田中智洋、今枝憲郎、中尾一和
    • Organizer
      第43回日本神経内分泌学会学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2016-10-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Key role of dietary linoleic acid excess in obesity - a lipidomics-based analysis2016

    • Author(s)
      T Tanaka, M Inoue, T Sonoyama, Y Ogino, T Guo, H Koyama, T Unzai, K Imaeda, K Nakao
    • Organizer
      第37回日本肥満学会(The 37th Annual Meeting of Japan Siciety for the Study of Obesity)、Japan Korea Taiwan(JKT) Joint Symposium
    • Place of Presentation
      東京
    • Year and Date
      2016-10-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高脂肪食による視床下部リピドーム変化の病態生理的意義2016

    • Author(s)
      田中智洋、井上雅文、園山拓洋、荻野陽平、Tingting Guo、小山博之、今枝憲郎、中尾一和
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Dynamism of the Hypothalamic Transcriptome Uncovers “Stages” during the Development of Diet-Induced Obesity in Mice2016

    • Author(s)
      T Tanaka, T Sonoyama, H.Sawada, M.Inoue, Y Ogino, T Guo, K Nakao
    • Organizer
      European Obesity Summit
    • Place of Presentation
      Gothenburg ( Sweden)
    • Year and Date
      2016-06-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 統合オミクス解析から迫る肥満の視床下部障害の分子実態2016

    • Author(s)
      田中智洋
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-04-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited

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

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