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Analysis of the Control Mechanism of Age-related Diseases by GADD34

Research Project

Project/Area Number 19K11687
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionSaitama University

Principal Investigator

Nishio Naomi  埼玉大学, 教育学部, 准教授 (80513457)

Co-Investigator(Kenkyū-buntansha) 磯部 健一  修文大学, 医療科学部, 教授 (20151441)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsGADD34 / 老化 / 肝臓 / 糖質代謝 / 脂質代謝 / インスリンシグナル伝達系 / インスリン抵抗性 / JNK / NASH / インスリンレセプターシグナル伝達系 / 炎症 / 栄養 / シグナル伝達系 / 免疫
Outline of Research at the Start

GADD34は老化、代謝、炎症に関連する3つのシグナル伝達系を同時に制御すると考えられる。そこで本研究では、GADD34 KOマウスを老化に伴って発症する炎症性疾患及びメタボリックシンドロームのモデルマウスとして、栄養の摂取、慢性炎症などの条件を与え、GADD34がこれらのシグナル伝達系を制御するメカニズムを検索することによって、メタボリックシンドロームの予防、治療、さらに、老化の予防に結びつけることを目標に研究を行う。

Outline of Final Research Achievements

In this study, we investigated the mechanisms the of fatty liver disease, a cause of age-related diseases, in GADD34 gene knockout (KO) mice by examining glucose and lipid metabolism in the liver. Our examination of fatty liver formation revealed that fatty liver disease is less likely to develop with lipid overconsumption alone and that the presence of carbohydrates is necessary. In KO mice, in addition to the previously reported hyperactivation of the insulin signaling pathway, both lipid and glucose metabolism are enhanced in the liver, making fatty liver formation more likely. Furthermore, we found that the inflammatory signaling pathway is also enhanced in the liver of KO mice, putting them at a higher risk for developing NASH and insulin resistance.

Academic Significance and Societal Importance of the Research Achievements

GADD34遺伝子欠損マウスを老化関連疾患発症のモデルとして解析することで、小胞体ストレスにおける役割以外は明確になっていなかったGADD34の役割は、老化におけるシグナル伝達系や代謝系にも関与していることが明らかとなった。このように老化関連疾患の発症メカニズムを解明することは、老化に伴って発症する疾患を抑制する可能性が示唆される。日本は超高齢化社会で、高齢者の健康は社会的にも個人的にも重要な課題である。老化は必然であるが健康に老化することが可能となれば、社会的な医療費抑制につながるだけでなく高齢者の尊厳ある生活の維持が可能となると考えている。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (5 results)

  • [Journal Article] Hen egg only diets support healthy aging in adult mice2023

    • Author(s)
      Naomi Nishio, Ken-ich Isobe
    • Journal Title

      Journal of Animal Physiology and Animal Nutrition

      Volume: - Issue: 4 Pages: 1110-1124

    • DOI

      10.1111/jpn.13805

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hen-egg suppresses fatty liver induced by sugar, glucose or fructose.2021

    • Author(s)
      Ken-ichi Isobe, Rena Suzuki, Kana Kato, Miki Kawai, Ami Kuzuya, Aoi Kanjya, Chiaki Suitou, Yui Nakano, Manae Nagasaki, Aki Hatanaka, Asuka Konno and Naomi Nishio
    • Journal Title

      Journal of Lipid Nutrition

      Volume: 30 Pages: 1-17

    • NAID

      130008049519

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Are Mice Born Normally With an Egg-only Diet?2020

    • Author(s)
      Ken-ichi Isobe, Naomi Nishio
    • Journal Title

      Biomedical Research and Reviews

      Volume: 3.4 Pages: 1-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Complete Genome Sequence of emm1 Streptococcus pyogenes 10-85, a Strain Isolated from a Patient with Streptococcal Toxic Shock Syndrome in Japan.2019

    • Author(s)
      Tatsuno I, Isaka M, Matsumoto M, Nishio N, Matsui H, Hasegawa T.
    • Journal Title

      Microbiol Resour Announc

      Volume: 13 Issue: 24

    • DOI

      10.1128/mra.00453-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] GADD34発現の老化による変化;KOマウスを使用した解析2023

    • Author(s)
      西尾尚美、磯部健一、長谷川忠男
    • Organizer
      第46回日本基礎老化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] GADD34 の機能解析2022

    • Author(s)
      磯部健一、長谷川忠男、○西尾尚美
    • Organizer
      第16回 日本臨床検査学教育学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Adult mice fed only heneggs are alive healthy until aged, but pups nursed by egg-only mice died early.2022

    • Author(s)
      Naomi Nishio, Ken-ich Isobe
    • Organizer
      第45回日本基礎老化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Adult mice fed only heneggs are alive healthy until aged, but pups nursed by egg-only mice died early.2022

    • Author(s)
      NAOMI Nishio, KEN-ICHI Isobe
    • Organizer
      日本基礎老化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Mice fed only heneggs are alive healthy until aged.2021

    • Author(s)
      NAOMI Nishio, KEN-ICHI Isobe
    • Organizer
      日本基礎老化学会
    • Related Report
      2021 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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