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Elucidation of molecular mechanisms of muscle atrophy and exercise caused by FOXO1 and PGC1alpha

Research Project

Project/Area Number 16H04926
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionKyoto Prefectural University

Principal Investigator

Kamei Yasutomi  京都府立大学, 生命環境科学研究科, 教授 (70300829)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords骨格筋 / 筋萎縮 / 運動 / 生活習慣病 / 筋再生 / エピジェネティクス / アミノ酸 / 遺伝子発現 / 転写調節因子
Outline of Final Research Achievements

Skeletal muscle plays important roles in exercise, energy expenditure, and glucose/amino acid metabolism. Understanding the molecular mechanisms underlying muscle metabolism during atrophy, which seriously impairs human health and the quality of life, is important for developing methods to prevent these conditions. In this study, we have investigated the mechanisms of muscle metabolism in vivo and in vitro, with focus on FOXO1 and PGC1α/PGC1β as major regulators. We found that vitamin D may prevent muscle atrophy through the FOXO1-mediated pathway in muscle cells. Additionally, soy-derived isoflavones activated PGC1β and increased the expression of energy expenditure genes. Furthermore, we have evaluated the possible involvement of DNA methylation, a major mechanism of epigenetic regulation, in the muscle atrophy/regeneration process. Our findings could provide a practical foundation to develop functional foods that target atrophy and/or obesity.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会を迎えた我が国において、骨格筋機能の向上は健康寿命の延長の観点から重要である。本研究では、FOXO1とPGC1αという2つの因子に着目して、標的遺伝子の探索と分子機序・機能解析を行った。筋萎縮と運動能改善における遺伝子発現制御を調べ、さらに食品成分が及ぼす影響を解析した。その結果、ビタミンDが骨格筋萎縮抑制、大豆イソフラボンがエネルギー消費を促進するというデータが得られた。また筋萎縮・筋再生低下におけるDNAメチル化の関与が示唆された。本研究の成果は、筋萎縮予防・筋機能向上のための機能性食品や医薬品の開発につながるものである。

Report

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

    (32 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results) Remarks (3 results)

  • [Int'l Joint Research] University of Maryland(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Chongqing Medical University(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Maryland(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Genistein, daidzein, and resveratrols stimulate PGC-1β-mediated gene expression2019

    • Author(s)
      Uchitomi Ran、Nakai Shiho、Matsuda Rintaro、Onishi Takumi、Miura Shinji、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 17 Pages: 51-55

    • DOI

      10.1016/j.bbrep.2018.11.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of long-term physical exercise on skeletal muscles in senescence-accelerated mice (SAMP8)2018

    • Author(s)
      Takigawa Kaho、Matsuda Rintaro、Uchitomi Ran、Onishi Takumi、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 83 Issue: 3 Pages: 518-524

    • DOI

      10.1080/09168451.2018.1547625

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitamin D Attenuates FOXO1-Target Atrophy Gene Expression in C2C12 Muscle Cells2018

    • Author(s)
      HIROSE Yuma、ONISHI Takumi、MIURA Shinji、HATAZAWA Yukino、KAMEI Yasutomi
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 64 Issue: 3 Pages: 229-232

    • DOI

      10.3177/jnsv.64.229

    • NAID

      130007413183

    • ISSN
      0301-4800, 1881-7742
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood2018

    • Author(s)
      X Yuan, K Tsujimoto, K Hashimoto, K Kawahori, N Hanzawa, M Hamaguchi, T Seki, M Nawa, T Ehara, Y Kitamura, I Hatada, M Konishi, N Itoh, Y Nakagawa, H Shimano, T Takai-Igarashi, Y Kamei, Y Ogawa.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 636-636

    • DOI

      10.1038/s41467-018-03038-w

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PGC-1α regulates alanine metabolism in muscle cells.2018

    • Author(s)
      Hatazawa Y, Qian K, Gong DW, Kamei Y.
    • Journal Title

      PLoS One

      Volume: 13(1) Issue: 1 Pages: e0190904-e0190904

    • DOI

      10.1371/journal.pone.0190904

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration2018

    • Author(s)
      Hatazawa Yukino、Ono Yusuke、Hirose Yuma、Kanai Sayaka、Fujii Nobuharu L.、Machida Shuichi、Nishino Ichizo、Shimizu Takahiko、Okano Masaki、Kamei Yasutomi、Ogawa Yoshihiro
    • Journal Title

      The FASEB Journal

      Volume: 32 Issue: 3 Pages: 1452-1467

    • DOI

      10.1096/fj.201700573r

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition.2017

    • Author(s)
      Ishikawa T, Kitaura Y, Kadota Y, Morishita Y, Ota M, Yamanaka F, Xu M, Ikawa M, Inoue N, Kawano F, Nakai N, Murakami T, Miura S, Hatazawa Y, Kamei Y, Shimomura Y.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 39825-39825

    • DOI

      10.1038/srep39825

    • NAID

      120006957417

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deletion of the transcriptional coactivator PGC1α in skeletal muscles is associated with reduced expression of genes related to oxidative muscle function.2016

    • Author(s)
      Hatazawa Y, Minami K, Yoshimura R, Onishi T, Manio MC, Inoue K, Sawada N, Suzuki O, Miura S, Kamei Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 481 Issue: 3-4 Pages: 251-258

    • DOI

      10.1016/j.bbrc.2016.10.133

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] FOXO1 delays skeletal muscle regeneration and suppresses myoblast proliferation.2016

    • Author(s)
      Yamashita A, Hatazawa Y, Hirose Y, Ono Y, Kamei Y.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 80 Issue: 8 Pages: 1531-5

    • DOI

      10.1080/09168451.2016.1164585

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phosphorylation of 4EBP by oral leucine administration was suppressed in the skeletal muscle of PGC-1α knockout mice.2016

    • Author(s)
      Yoshimura R, Minami K, Matsuda J, Sawada N, Miura S, Kamei Y.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 80(2) Issue: 2 Pages: 288-90

    • DOI

      10.1080/09168451.2015.1083397

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity.2015

    • Author(s)
      Morita S, Nakabayashi K, Kawai T, Hayashi K, Horii T, Kimura M, Kamei Y, Ogawa Y, Hata K, Hatada I
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 21693-21693

    • DOI

      10.1038/srep21693

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 筋萎縮時にDNAメチル化酵素Dnmt3aの低下は筋再生を抑制する2018

    • Author(s)
      亀井康富、畑澤幸乃、小野悠介、岡野正樹、小川佳宏
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 遺伝子改変マウスを用いた骨格筋アミノ酸代謝の解析2018

    • Author(s)
      亀井康富、畑澤幸乃、三浦進司
    • Organizer
      日本筋学会第4回学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 老化促進モデルマウス(SAMP8)の筋機能低下に対する長期的な運動の効果2018

    • Author(s)
      亀井康富、瀧川花穂、松田凛太郎、畑澤幸乃
    • Organizer
      第33回老化促進モデルマウス(SAM)学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] サルコペニアの筋再生低下におけるDNAメチル化制御2018

    • Author(s)
      亀井康富、畑澤幸乃、瀧川花穂、岡野正樹、小野悠介、小川佳宏
    • Organizer
      第39回日本肥満学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Reduced Dnmt3a Increases Gdf5 Expression with Suppressed Satellite Cell Differentiation and Impaired Skeletal Muscle Regeneration2018

    • Author(s)
      亀井康富
    • Organizer
      Asia Pacific Nutrigenomics Nutrigenetics Organisation 2018 Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DNAメチル化による遺伝子発現調節を介した代謝制御2017

    • Author(s)
      亀井康富
    • Organizer
      日本農芸化学会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Gene regulation in skeletal muscle function; atrophy and exercise2017

    • Author(s)
      亀井康富
    • Organizer
      International Conference on Functional Food for Metabolic Homeostasis in Aging
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DNAメチル化による遺伝子発現調節を介した代謝制御2017

    • Author(s)
      亀井康富
    • Organizer
      日本農芸化学会2017年度大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Deletion of the transcriptional coactivator PGC1α in skeletal muscles is associated with reduced expression of genes related to oxidative muscle function2017

    • Author(s)
      Yasutomi Kamei, Yukino Hatazawa, Kimiko Minami, Ryoji Yoshimura, Takumi Onishi, Naoki Sawada, Shinji Miura
    • Organizer
      Experimental Biology 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] L-シトルリンにより転写共役因子PGC1αを介してマウス骨格筋の血管数が増加した2017

    • Author(s)
      亀井康富、森本茉穂、大西拓己、鈴木貴視、森田匡彦、畑澤幸乃
    • Organizer
      第71回日本栄養・食糧学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨格筋アミノ酸代謝における遺伝子発現制御2017

    • Author(s)
      亀井康富、三浦進司
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨格筋機能と肥満改善における転写制御因子の役割2016

    • Author(s)
      亀井康富、三浦進司、小川佳宏
    • Organizer
      第37回日本肥満学会 シンポジウム
    • Place of Presentation
      東京ファッションタウン(東京都江東区)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ロコモーティブシンドロームと栄養、骨格筋機能におけるアミノ酸代謝の役割と分子機序2016

    • Author(s)
      亀井康富、三浦進司
    • Organizer
      第70回 日本栄養・食糧学会大会 シンポジウム
    • Place of Presentation
      武庫川女子大学(兵庫県西宮市)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 抗ロコモのためのニュートリジェネティクス的解析と栄養・食糧科学の最前線、骨格筋機能と分子栄養学2016

    • Author(s)
      亀井康富
    • Organizer
      第34回日本骨代謝学会学術集会・第3回アジア太平洋骨代謝学会議
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨格筋における核内受容体・転写共役因子と生活習慣病2016

    • Author(s)
      亀井康富
    • Organizer
      第24回日本ステロイドホルモン学会 シンポジウム
    • Place of Presentation
      ホルトホール大分(大分県大分市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://nutrition.life.kpu.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都府立大学大学院生命環境科学研究科分子栄養学研究室

    • URL

      http://nutrition.life.kpu.ac.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都府立大学生命環境科学研究科分子栄養学研究室

    • URL

      http://nutrition.life.kpu.ac.jp/

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2022-05-20  

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