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The functions of TFG in adipocytes, small intestine and hepatocytes and its involvement in metabolic disorders

Research Project

Project/Area Number 19K17986
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionHiroshima University

Principal Investigator

Yamamotoya Takeshi  広島大学, 医系科学研究科(医), 助教 (50760013)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords糖尿病 / 脂肪細胞 / 脂肪肝 / 糖・脂質代謝 / 細胞内小胞輸送 / 肥満 / 脂質代謝
Outline of Research at the Start

Trk-fused gene (TFG) は肥満において脂肪組織でその発現量が増加することから、脂肪組織の増大に重要な可能性が示唆される。実際、脂肪細胞特異的TFG KOマウスでは高脂肪食を与えた際の脂肪組織増大が抑制され、その代わりに脂肪肝が悪化し、耐糖能障害を呈する。本研究ではそのメカニズムを解明するとともに、小腸における脂肪吸収や、肝臓での脂質制御におけるTFGの役割の解明も試みる。

Outline of Final Research Achievements

The abundance of Trk-fused gene (TFG) in white adipose tissues drastically increases in obesity. In adipocyte-specific TFG knockout mice, adipocyte dysfunction was apparent judging from downregulation of PPARγ activity in adipocytes and subsequent hepatic steatosis. However, short-term TFG deletion in culture cells or in primary adipocytes derived from adipose tissue stromal vascular fraction (SVF) did not result in PPARγ downregulation, which led us consider that the significance of TFG in adipocyte was cell-size dependent. Moreover, we found that hepatocyte-specific TFG knockout mice also displayed hepatic steatosis, which seemed attributable to insufficient induction of PPARα target genes during fasting.

Academic Significance and Societal Importance of the Research Achievements

過剰な摂取エネルギーを適切に脂肪細胞に蓄えることは、脂肪肝などインスリン抵抗性の原因となる異所性脂肪蓄積を防ぎ、糖尿病の発症を抑えるために重要である。生体における脂肪細胞の適切な肥大に脂肪細胞のTFGが不可欠であること、また脂肪肝の抑制に肝細胞のTFGが重要であることが本研究で明らかとなった。その詳細なメカニズムについては現在検討中であるが、将来的に糖尿病や脂肪肝に対する新規治療薬の開発に繋がる可能性が期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Involvement of neuronal and muscular Trk-fused gene (TFG) defects in the development of neurodegenerative diseases2022

    • Author(s)
      Yamamotoya Takeshi、Hasei Shun、Akasaka Yasuyuki、Ohata Yukino、Nakatsu Yusuke、Kanna Machi、Fujishiro Midori、Sakoda Hideyuki、Ono Hiraku、Kushiyama Akifumi、Misawa Hidemi、Asano Tomoichiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1966-1966

    • DOI

      10.1038/s41598-022-05884-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target2021

    • Author(s)
      Yamamotoya T, Nakatsu Y, Kanna M, Hasei S, Ohata Y, Encinas J, Ito H, Okabe T, Asano T, Sakaguchi T.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 18581-18581

    • DOI

      10.1038/s41598-021-97972-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes2021

    • Author(s)
      Fujishiro Midori、Ishihara Hisamitsu、Ogawa Katsuhiko、Murase Takayo、Nakamura Takashi、Watanabe Kentaro、Sakoda Hideyuki、Ono Hiraku、Yamamotoya Takeshi、Nakatsu Yusuke、Asano Tomoichiro、Kushiyama Akifumi
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 8 Pages: 1052-1052

    • DOI

      10.3390/biomedicines9081052

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological Role of Pin1 in the Development of DSS-Induced Colitis2021

    • Author(s)
      Matsunaga Yasuka、Hasei Shun、Yamamotoya Takeshi、Honda Hiroaki、Kushiyama Akifumi、Sakoda Hideyuki、Fujishiro Midori、Ono Hiraku、Ito Hisanaka、Okabe Takayoshi、Asano Tomoichiro、Nakatsu Yusuke
    • Journal Title

      Cells

      Volume: 10 Issue: 5 Pages: 1230-1230

    • DOI

      10.3390/cells10051230

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Carnosic Acid and Carnosol Activate AMPK, Suppress Expressions of Gluconeogenic and Lipogenic Genes, and Inhibit Proliferation of HepG2 Cells2021

    • Author(s)
      Hasei S, Yamamotoya T, Nakatsu Y, Ohata Y, Itoga S, Nonaka Y, Matsunaga Y, Sakoda H, Fujishiro M, Kushiyama A, Asano T.
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 8 Pages: 4040-4040

    • DOI

      10.3390/ijms22084040

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolyl isomerase Pin1 interacts with adipose triglyceride lipase and negatively controls both its expression and lipolysis2021

    • Author(s)
      Yusuke Nakatsu, Takeshi Yamamotoya, Mizuki Okumura, Tetsuhiro Ishii, Mayu Kanamoto, Miki Naito, Mikako Nakanishi, Shunya Aoyama, Yasuka Matsunaga, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Tomoichiro Asano
    • Journal Title

      Metabolism

      Volume: 15 Pages: 154459-154459

    • DOI

      10.1016/j.metabol.2020.154459

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolyl isomerase Pin1 in metabolic reprogramming of cancer cells2020

    • Author(s)
      Nakatsu Yusuke、Yamamotoya Takeshi、Ueda Koji、Ono Hiraku、Inoue Masa-Ki、Matsunaga Yasuka、Kushiyama Akifumi、Sakoda Hideyuki、Fujishiro Midori、Matsubara Akio、Asano Tomoichiro
    • Journal Title

      Cancer Letters

      Volume: 470 Pages: 106-114

    • DOI

      10.1016/j.canlet.2019.10.043

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pin1 Plays Essential Roles in NASH Development by Modulating Multiple Target Proteins2019

    • Author(s)
      Inoue Masa-Ki、Nakatsu Yusuke、Yamamotoya Takeshi、Hasei Shun、Kanamoto Mayu、Naitou Miki、Matsunaga Yasuka、Sakoda Hideyuki、Fujishiro Midori、Ono Hiraku、Kushiyama Akifumi、Asano Tomoichiro
    • Journal Title

      Cells

      Volume: 8 Issue: 12 Pages: 1545-1545

    • DOI

      10.3390/cells8121545

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice2019

    • Author(s)
      Mizuno Yu、Yamamotoya Takeshi、Nakatsu Yusuke、Ueda Koji、Matsunaga Yasuka、Inoue Masa-Ki、Sakoda Hideyuki、Fujishiro Midori、Ono Hiraku、Kikuchi Takako、Takahashi Masahiro、Morii Kenichi、Sasaki Kensuke、Masaki Takao、Asano Tomoichiro、Kushiyama Akifumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 19 Pages: 4680-4680

    • DOI

      10.3390/ijms20194680

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice2019

    • Author(s)
      Inoue Masa-Ki、Matsunaga Yasuka、Nakatsu Yusuke、Yamamotoya Takeshi、Ueda Koji、Kushiyama Akifumi、Sakoda Hideyuki、Fujishiro Midori、Ono Hiraku、Iwashita Misaki、Sano Tomomi、Nishimura Fusanori、Morii Kenichi、Sasaki Kensuke、Masaki Takao、Asano Tomoichiro
    • Journal Title

      Diabetology & Metabolic Syndrome

      Volume: 11 Issue: 1 Pages: 57-57

    • DOI

      10.1186/s13098-019-0454-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 骨格筋TFGの肥満形成および神経筋接合部の維持における役割2022

    • Author(s)
      山本屋 武, 大畠 侑乃, 赤坂 保行, 神名 麻智, 中津 祐介, 迫田 秀之, 藤城 緑, 櫛山 暁史, 浅野 知一郎
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Trk-fused gene (TFG) の脂肪細胞における代謝制御機構の解明2021

    • Author(s)
      山本屋 武, 長谷井 竣, 中津 祐介, 大畠 侑乃, 迫田 秀之, 藤城 緑, 櫛山 暁史, 浅野 知一郎
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脂肪細胞のTrk-fused gene (TFG) はPPARγ発現量およびミトコンドリア機能を調節し, adipose expansionに重要である2020

    • Author(s)
      山本屋 武、長谷井 竣、中津 祐介、迫田 秀之、藤城 緑、櫛山 暁史、浅野 知一郎
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Trk-fused gene (TFG) の骨格筋機能および肥満発症における役割2020

    • Author(s)
      長谷井 竣, 山本屋 武, 中津 祐介, 迫田 秀之, 藤城 緑, 櫛山 暁史, 浅野 知一郎
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Pin1 and Trk-fused gene (TFG): novel regulators for β-cell mass and function2019

    • Author(s)
      Takeshi Yamamotoya, Yusuke Nakatsu, Akifumi Kushiyama, Hisamitsu Ishihara, Tomoichiro Asano
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 脂肪細胞のTrk-fused gene (TFG) による代謝制御機構の解明2019

    • Author(s)
      山本屋 武、長谷井 竣、中津 祐介、井上 賢紀、迫田 秀之、藤城 緑、櫛山 暁史、浅野 知一郎
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脂肪細胞のTrk-fused gene (TFG) による代謝制御機構の解明2019

    • Author(s)
      山本屋 武、長谷井 竣、中津 祐介、井上 賢紀、櫛山 暁史、浅野 知一郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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