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Mechanism of the beneficial effects of maternal exercise on next generation health focusing on maternal organs, placenta, and fetal tissues

Research Project

Project/Area Number 21H03315
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59020:Sports sciences-related
Research InstitutionTokyo Medical and Dental University (2022-2023)
Tohoku University (2021)

Principal Investigator

Kusuyama Joji  東京医科歯科大学, 大学院医歯学総合研究科, テニュアトラック准教授 (70596105)

Co-Investigator(Kenkyū-buntansha) 永富 良一  東北大学, 医工学研究科, 教授 (20208028)
木村 友彦  川崎医科大学, 医学部, 講師 (50454830)
小塚 智沙代  国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (70722370)
長名 シオン  東北大学, 医工学研究科, 特任助教 (60868131)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords妊娠期運動 / 胎盤 / プラセントカイン / エクサカイン / SOD3 / 肥満 / 糖尿病 / 習慣的運動 / 妊娠 / 運動 / エピジェネティクス / 肝臓 / 糖代謝 / 脂肪組織 / エピゲノム / ビタミンD / 次世代
Outline of Research at the Start

妊婦の肥満や糖尿病は、子に対して糖尿病をはじめとした慢性代謝性疾患の発症リスクを伝播させる。我々は妊娠期の運動はこの悪循環を防ぐ有用な方法であり、運動刺激を受容した胎盤が分泌するタンパク質が運動効果を伝達することで、仔の糖代謝を正常化していることを明らかにした。しかし、母体がどのように運動効果を胎盤に伝達して胎仔の臓器機能を制御しているのかは未解明である。本研究は、胎盤が母体環境を子に伝達する情報インターフェースであると仮説を立て、運動が子にもたらす有益性の次世代伝播経路の全容を解明し、次世代の健康を守る有効な運動プログラム、運動効果を予測可能なモニタリング開発によって実践的介入に繋げる。

Outline of Final Research Achievements

We previously reported that exercise during pregnancy affects fetal liver function through SOD3, a protein secreted by the placenta. This improves glucose metabolism in offspring and reduces obesity risk. Our study elucidated the molecular mechanism underlying these changes and highlighted the unique role of placenta-derived SOD3. Additionally, we found that exercise during pregnancy impacts glucose metabolism across three generations. Furthermore, we identified information transmission proteins between maternal organs and the placenta using genetically modified mice.

Academic Significance and Societal Importance of the Research Achievements

本研究は、妊娠期運動が子の将来的な健康に及ぼす根底的な分子機構を世界で初めて実証しました。また運動応答性臓器としての胎盤の重要な役割を明らかにし、新たな胎盤機能の存在を提唱しました。胎盤を通じて子の将来の健康を増進できれば、これまでにない次世代医療の実現に繋がる可能性があります。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (65 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (11 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (40 results) (of which Int'l Joint Research: 10 results,  Invited: 26 results) Remarks (7 results)

  • [Int'l Joint Research] ジョスリン糖尿病センター/テキサス大学/コロラド大学(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] オーフス大学(デンマーク)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ジョスリン糖尿病センター/テキサス大学/コロラド大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] オーフス大学(デンマーク)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] オタワ大学(カナダ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] アイルランガ大学(インドネシア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] ジョスリン糖尿病センター/テキサス大学/コロラド大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] オーフス大学(デンマーク)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] シンガポール国立大学(シンガポール)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] オタワ大学(カナダ)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation2022

    • Author(s)
      Sugimoto Satoru、Mena Hebe Agustina、Sansbury Brian E.、Kobayashi Shio、Tsuji Tadataka、Wang Chih-Hao、Yin Xuanzhi、Huang Tian Lian、Kusuyama Joji、...、Tseng Yu-Hua
    • Journal Title

      Nature Metabolism

      Volume: 4 Issue: 6 Pages: 775-790

    • DOI

      10.1038/s42255-022-00590-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HIF‐1α plays an essential role in BMP9‐mediated osteoblast differentiation through the induction of a glycolytic enzyme, PDK12022

    • Author(s)
      Amir Muhammad Subhan、Chiba Norika、Seong Chang Hwan、Kusuyama Joji、Eiraku Nahoko、Ohnishi Tomokazu、Nakamura Norifumi、Matsuguchi Tetsuya
    • Journal Title

      Journal of Cellular Physiology

      Volume: 237 Issue: 4 Pages: 2183-2197

    • DOI

      10.1002/jcp.30752

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Grandmaternal exercise improves metabolic health of second-generation offspring2022

    • Author(s)
      Alves-Wagner Ana B.、Kusuyama Joji、Nigro Pasquale、Ramachandran Krithika、Makarewicz Nathan、Hirshman Michael F.、Goodyear Laurie J.
    • Journal Title

      Molecular Metabolism

      Volume: 60 Pages: 101490-101490

    • DOI

      10.1016/j.molmet.2022.101490

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Maternal Exercise-Induced SOD3 Reverses the Deleterious Effects of Maternal High Fat Diet on Offspring Metabolism Through Stabilization of H3K4me3 and Protection Against WDR82 Carbonylation2022

    • Author(s)
      Kusuyama Joji、Makarewicz Nathan S.、Albertson Brent G.、Alves-Wagner Ana Barbara、Conlin Royce H.、Prince Noah B、Alves Christiano R. R.、Ramachandran Krithika、Kozuka Chisayo、Xiudong Yang、Xia Yang、Hirshman Michael F.、Hatta Toshihisa、Nagatomi Ryoichi、Nozik Eva S.、Goodyear Laurie J.
    • Journal Title

      Diabetes

      Volume: - Issue: 6 Pages: 1170-1181

    • DOI

      10.2337/db21-0706

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Aerobic and Resistant Exercise Intervention on Inflammaging of Type 2 Diabetes Mellitus in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis2022

    • Author(s)
      Xing Huimin、Lu Jinhua、Yoong Si Qi、Tan Yue Qian、Kusuyama Joji、Wu Xi Vivien
    • Journal Title

      Journal of the American Medical Directors Association

      Volume: 23 Issue: 5 Pages: 823-830.e13

    • DOI

      10.1016/j.jamda.2022.01.055

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bromodomain Inhibition Reveals FGF15/19 as a Target of Epigenetic Regulation and Metabolic Control2022

    • Author(s)
      Kozuka C, Efthymiou V, Sales VM, Zhou L, Osataphan S, Yuchi Y, Chimene-Weiss J, Mulla C, Isganaitis E, Desmond J, Sanechika S, Kusuyama J, Goodyear L, Shi X, Gerszten RE, Aguayo-Mazzucato C, Carapeto P, Teixeira SD, Sandoval D, Alonso-Curbelo D, Wu L, Qi J, Patti ME.
    • Journal Title

      Diabetes

      Volume: - Issue: 5 Pages: 1023-1033

    • DOI

      10.2337/db21-0574

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health2021

    • Author(s)
      Kusuyama J, Alves-Wagner AB, Conlin RH, Makarewicz NS, Albertson BG, Prince NB, Kobayashi S, Kozuka C, Moller M, Bjerre M, Fuglsang J, Miele E, Middelbeek RJW, Xiudong Y, Xia Y, Garneau L, Bhattacharjee J, Aguer C, Patti ME, Hirshman MF, Jessen N, Hatta T, Ovesen PG, Adamo KB, Nozik-Grayck E, Goodyear LJ.
    • Journal Title

      Cell Metabolism

      Volume: Mar 19 Issue: 5 Pages: 939-956

    • DOI

      10.1016/j.cmet.2021.03.004

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 胎盤を介した妊娠期運動情報の次世代伝播機構2024

    • Author(s)
      楠山 譲二
    • Organizer
      5th Joint Diabetes Conference
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 胎盤における運動とビタミンDの協調シグナルによる運動情報の次世代伝播2023

    • Author(s)
      楠山 譲二
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 胎盤を介した運動情報の次世代伝播による子の肥満予防機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      第44回日本肥満学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 胎盤における運動とビタミンDの協調シグナルは子の糖代謝能を制御する2023

    • Author(s)
      楠山 譲二
    • Organizer
      第31回日本胎盤学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ビタミンDとプラセントカインを介した運動情報の次世代伝播機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Placental transmission of maternal information to offspring2023

    • Author(s)
      Joji Kusuyama
    • Organizer
      Children's Hospital Colorado Research Seminar
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 胎盤における運動とビタミンDの協調シグナルは子の糖代謝能を制御する2023

    • Author(s)
      楠山 譲二
    • Organizer
      第11回日本DOHaD学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 母親の生活習慣の次世代伝播機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      第30回西日本肥満研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 妊娠期運動効果の次世代伝播機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      第2回 昭和大学薬理科学研究センター主催セミナー, 昭和大学学士会後援セミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ビタミンDによる運動情報の次世代伝播機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      第66回日本糖尿病学会年次学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ビタミンDによる運動情報の次世代伝播機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      第5回がんと代謝研究会・若手の会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 胎盤を介した運動情報の次世代伝播機構2023

    • Author(s)
      楠山 譲二
    • Organizer
      東京都立大学人間健康科学研究科ヘルスプロモーション学域特別講義
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 運動惹起性プラセントカインの発現調節と経世代情報伝達2023

    • Author(s)
      楠山 譲二
    • Organizer
      第27回日本心血管内分泌代謝学会学術総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 両親と子の性差から考える運動情報の次世代伝播機構2022

    • Author(s)
      楠山 譲二
    • Organizer
      第16回日本性差医学・医療学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ビタミンDによる運動惹起性プラセントカインの発現調節と経世代情報伝達2022

    • Author(s)
      楠山 譲二
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 運動惹起性胎盤由来SOD3はH3K4me3安定化とWDR82カルボニル化を防ぐことで母親の高脂肪食摂取で誘導される子の糖代謝能悪化を防ぐ2022

    • Author(s)
      楠山 譲二
    • Organizer
      第30回日本胎盤学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 妊娠期運動効果の次世代伝播と子の糖代謝向上効果2022

    • Author(s)
      楠山 譲二
    • Organizer
      第20回国際SHR(Japanese Socieity for Hypertension Related Disease Model Research)シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 胎盤由来 SOD3は胎児肝臓のH3K4me3レベルを安定化させることで子の糖代謝能を向上させる2022

    • Author(s)
      楠山 譲二
    • Organizer
      第9回 日本DOHaD学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 妊娠期運動による子の肥満予防効果を規定するエピジェネティクス調節機構2022

    • Author(s)
      楠山 譲二
    • Organizer
      第77回 日本体力医学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎盤情報伝達の基盤解明と臨床応用をめざす国際共同研究2022

    • Author(s)
      楠山 譲二
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 妊娠期運動効果の次世代伝播機構2022

    • Author(s)
      楠山 譲二
    • Organizer
      第12回分子骨格筋代謝研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Placental Superoxide Dismutase 3 Mediates Benefits of Maternal Exercise on Offspring Health2022

    • Author(s)
      Joji Kusuyama
    • Organizer
      27th Annual Congress of the European College of Sport Science
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 第62回日本先天異常学会学術集会2022

    • Author(s)
      楠山 譲二
    • Organizer
      胎盤による母体情報の次世代伝達機構
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Molecular Mechanisms of Exercise That can Transform and Improve our Future Health2022

    • Author(s)
      Joji Kusuyama
    • Organizer
      2022 IADR (International Association for Dental Research) /APR (Association for Dental Research Asia Pacific Region) General Session
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 母親と父親の運動効果は子にどのように伝達されるか?~げっ歯類モデル研究から~2021

    • Author(s)
      楠山 譲二
    • Organizer
      第94回 日本内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] How engaging in exercise can transform and improve our health2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      Stovit Online Series (SOS)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Beneficial Effects of Exercise in the Middle Age on Metabolic Health Outcomes in Aging2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      MIRAI2.0 Digital Research and Innovation Week 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Placental Superoxide Dismutase 3 Mediates Benefits of Maternal Exercise on Offspring Health2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      Nature Conference, Metabolism in Health and Disease
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 胎盤由来SOD3を介した妊娠期運動による肥満予防効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      第61回日本先天異常学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Placental Superoxide Dismutase 3 Mediates Benefits of Maternal Exercise on Offspring Health2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      the 2021 meeting of the International Federation of Placenta Associations (IFPA)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胎盤由来 SOD3 を介した妊娠期運動による肥満予防効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      第45回日本女性栄養・代謝学会学術集会・第10回日本DOHaD学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 胎盤由来 SOD3 を介した妊娠期運動による肥満予防効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      第76回日本体力医学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 次世代への運動情報伝達器官としての胎盤機能の新定義2021

    • Author(s)
      楠山 譲二
    • Organizer
      第63回歯科基礎医学会学術大会 歯科基礎アカデミーシンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Maternal Exercise Improve Offspring Metabolic Health through Epigenetic Changes Mediated by a Novel Placenta-Derived Protein2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      2021 International Conference of the Korean Society of Exercise Physiology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 胎盤由来 SOD3 を介した妊娠期運動による肥満予防効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      第29回日本胎盤学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Exercising for future generations2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      Kyudai Oral Bioscience & OBT Research Center 5th Joint International Symposium 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 妊娠期運動・栄養による胎盤由来SOD3を介した肥満予防効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 妊娠期運動効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      日本生物物理学会北海道支部セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Maternal exercise improve offspring metabolic health through a novel placentokine2021

    • Author(s)
      Joji Kusuyama
    • Organizer
      77th IRCMS seminar Mini Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 妊娠期運動の胎盤由来SOD3を介した肥満予防効果の次世代伝播機構2021

    • Author(s)
      楠山 譲二
    • Organizer
      第42回日本肥満学会・第39回日本肥満症治療学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Remarks] 楠山 譲二 クスヤマ ジョウジ (Joji Kusuyama)

    • URL

      https://researchmap.jp/JojiKusuyama

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Remarks] 楠山研究室

    • URL

      https://bsin.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 新テニュアトラック教員採用者(2022年10月1日付)一覧

    • URL

      https://www.tmd.ac.jp/cmn/yisc/tenuretrack.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 妊娠中の運動が子の肥満を防ぐ仕組みを解明

    • URL

      https://www.fris.tohoku.ac.jp/feature/topics/detail---id-1094.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 妊娠中の運動が産まれる子の肥満や糖尿病のリスクを低減 妊娠期の運動で次世代の健康も守れる

    • URL

      http://himan.jp/news/2022/000602.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 妊娠中の運動が子の肥満を防ぐ仕組みを解明

    • URL

      https://www.tohoku.ac.jp/japanese/2022/04/press20220411-01-protein.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 妊娠中の運動が胎盤を通じて子の肥満を防ぐ 胎盤・運動・栄養を活用した次世代の健康増進

    • URL

      https://www.tohoku.ac.jp/japanese/2021/04/press20210406-01-sod3.html

    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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