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Comprehensive phenotypic analysis of liver-specific Phgdh deficient mice

Research Project

Project/Area Number 15K12346
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Eating habits
Research InstitutionKagoshima University (2018)
Fukuoka Women's University (2015-2017)

Principal Investigator

Hamano Momoko  鹿児島大学, 医歯学総合研究科, 特任研究員 (40717336)

Co-Investigator(Kenkyū-buntansha) 古屋 茂樹  九州大学, 農学研究院, 教授 (00222274)
Research Collaborator Hamada Shun  
Project Period (FY) 2015-04-01 – 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsセリン / 肝臓 / 肥満 / 低タンパク質栄養 / アミノ酸代謝 / アミノ酸 / タンパク質栄養
Outline of Final Research Achievements

Previous study shows that the expression of serine synthesis enzyme Phgdh in the liver is maintained low level in steady state, but rapidly upregulated when fed with low protein diet. However, the nutritional and physiological significance of serine synthesis in liver is unknown. We aim to clarify the physiological significance of de novo Ser synthesis in liver, we generated the liver hepatocyte-specific Phgdh KO (LKO) mice. Moreover, we analyzed the comprehensive phenotype of LKO mice under artificially changing in nutritional status.

Academic Significance and Societal Importance of the Research Achievements

肥満は生活習慣病の最大のリスク要因であり、その対策が社会的に急がれている。肥満患者においてアミノ酸のインバランスが起きていることが報告されているが、肥満の結果アミノ酸インバランスが誘導されるのか、アミノ酸インバランスが肥満を誘導するのか分かっていない。さらに、アミノ酸代謝異常やアミノ酸代謝酵素の機能低下が肥満の原因とする報告は未だに少なく集積は不十分である。肥満を表現型とした生体の栄養状態と肝臓におけるセリン合成能の関連を明らかにすることは、代謝性疾患とアミノ酸代謝の連関を新規に定義付ける重要な知見であり、また、肥満の新規治療法の開発にも繋がる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Metformin treatment ameliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 1.2018

    • Author(s)
      Tanokashira D , Kurata E, Fukuokaya W, Kenshiro Kawabe, Takeuchi H,Kashiwada M, Nakazato M , Taguchi A.
    • Journal Title

      FEBS Open Bio

      Volume: 印刷中 Issue: 6 Pages: 914-922

    • DOI

      10.1002/2211-5463.12429

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adaptive response to L-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts2016

    • Author(s)
      Tomoko Sayano, Yuki Kawano, Wataru Kusada, Yashiho Arimoto, Kayoko Esaki, Momoko Hamano, Miyako Udono, Yoshinori Katakura, Takuya Ogawa, Hisanori Kato, Yoshio Hirabayashi, Shigeki Furuya
    • Journal Title

      FEBS Open Bio

      Volume: 6 Issue: 4 Pages: 303-316

    • DOI

      10.1002/2211-5463.12038

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脳内セリン充足度の低下 が脳高次機能障害を惹起する分子機序2018

    • Author(s)
      濱野桃子,佐藤和貴,河野唯,原口祐里奈,立川正憲,古屋茂樹
    • Organizer
      日本農芸化学会 2018 大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Comprehensive phenotypic analysis of liver hepatocyte-specific Phgdh deficient mice2017

    • Author(s)
      M. Hamamo, K. Esaki, K. Moriyasu, S. Mori, Y. Hirabayashi, S. Furuya
    • Organizer
      IUNS-International Congress of Nutrition 21st
    • Place of Presentation
      アルゼンチン(ブエノスアイレス)
    • Year and Date
      2017-10-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive phenotypic analysis of liver hepatocyte-specific Phgdh deficient mice2017

    • Author(s)
      Momoko Hamano, Kayoko Esaki, Kazuki Moriyasu, Shinya Mori, Yoshio Hirabayashi, Shigeki Furuya
    • Organizer
      IUNS 21th International Congress of Nutrition
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝臓代謝恒常性維持に おけるリン酸化経路セリン生合成の役割2017

    • Author(s)
      濱野桃子、江崎加代子、森安一樹、毛利紳哉、古屋茂樹
    • Organizer
      日本アミノ酸学会第11 回学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞外セリン制限は肝がん 細胞株にセリン合成能欠損細胞と類似した特徴的セリン欠乏応答を惹起する2016

    • Author(s)
      濱野桃子,佐矢野智子,小田裕昭,加藤久典,古屋茂樹
    • Organizer
      日本アミノ酸学会10周年記念大会
    • Place of Presentation
      東京(東京大学)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
  • [Presentation] 細胞内de novoセリン合成系欠損による酸化ストレス脆弱性惹起と炎症反応関連遺伝子発現誘導2016

    • Author(s)
      濱野桃子,佐矢野智子,有本八潮,川野裕輝,鵜殿美弥子,片倉喜範,小川拓哉,加藤久典,平林義雄,古屋茂樹
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      北海道札幌市札幌コンベンションセンター
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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