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Physiological functions of branched-chain amino acids as regulatory factors in mammals

Research Project

Project/Area Number 17H03817
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionChubu University (2019)
Nagoya University (2017-2018)

Principal Investigator

SHIMOMURA Yoshiharu  中部大学, 応用生物学部, 教授 (30162738)

Co-Investigator(Kenkyū-buntansha) 北浦 靖之  名古屋大学, 生命農学研究科, 講師 (90442954)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
KeywordsBCAA / BCKDH / BDK / mTORC1 / 骨格筋 / 脳神経 / マウス / 筋肉 / 分岐鎖アミノ酸 / 代謝調節 / コンディショナルノックアウト
Outline of Final Research Achievements

Branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) have drawn attention as metabolic regulators in cells due to the diverse physiological actions. In the present study, we elucidated the mechanism that branched-chain α-keto acid dehydrogenase kinase (BDK), a regulator of BCAA metabolism, is controlled by Ca ions in cells. In the studies using conditional BDK-KO mice, we demonstrated that chronically low levels of BCAAs in skeletal muscle resulted in enhanced reactivity of muscle mTORC1, and slow recovery of muscle glycogen after exercise. Furthermore, we suggested that chronically low levels of BCAAs in brain were responsible for neurological abnormality.

Academic Significance and Societal Importance of the Research Achievements

分岐鎖アミノ酸(BCAA)の代謝調節機構はBCAAの生理作用のメカニズムを解明する上で重要である。本研究において、CaイオンによってBCAA代謝が調節されることを証明したが、この機構はBCAA代謝の新たな調節機構であり、これにより運動などによる骨格筋BCAA代謝の亢進を説明できる。コンディショナルBDK欠損マウスを用いた研究により、骨格筋のタンパク質およびグリコーゲン代謝においてBCAAが深く関与していることを示唆するとともに、正常な脳機能を維持するためには十分なBCAAの供給が重要であることを証明した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (33 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (23 results) (of which Int'l Joint Research: 7 results,  Invited: 9 results)

  • [Int'l Joint Research] University of Kansas Medical Center(米国)

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

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 分岐鎖アミノ酸(BCAA)とインスリン抵抗性2019

    • Author(s)
      下村吉治、北浦靖之
    • Journal Title

      医学と薬学

      Volume: 76 Pages: 1595-1601

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Ca2+-dependent inhibition of branched-chain α-ketoacid dehydrogenase kinase by thiamine pyrophosphate2018

    • Author(s)
      Noguchi Seisuke、Kondo Yusuke、Ito Rina、Katayama Takahiro、Kazama Shunsuke、Kadota Yoshihiro、Kitaura Yasuyuki、Harris Robert A.、Shimomura Yoshiharu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 504 Issue: 4 Pages: 916-920

    • DOI

      10.1016/j.bbrc.2018.09.038

    • NAID

      120006554494

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physiological and pathological roles of branched-chain amino acids in the regulation of protein and energy metabolism and neurological functions2018

    • Author(s)
      Shimomura Yoshiharu、Kitaura Yasuyuki
    • Journal Title

      Pharmacological Research

      Volume: 133 Pages: 215-217

    • DOI

      10.1016/j.phrs.2018.05.014

    • NAID

      120006554495

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 分岐鎖アミノ酸の分解制御機構とその重要性について2018

    • Author(s)
      北浦 靖之, 下村 吉治
    • Journal Title

      生化学/公益社団法人日本生化学会

      Volume: 90 Pages: 234-237

    • NAID

      40021617573

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex2018

    • Author(s)
      Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
    • Journal Title

      PLoS Biology

      Volume: 16 Issue: 3 Pages: e2005090-e2005090

    • DOI

      10.1371/journal.pbio.2005090

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Branched-chain amino acids regulate type I tropocollagen and type III tropocollagen syntheses via modulation of mTOR in the skin.2017

    • Author(s)
      Yamane T, Morioka Y, Kitaura Y, Iwatsuki K, Shimomura Y, Oishi Y.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 82 Issue: 4 Pages: 611-615

    • DOI

      10.1080/09168451.2017.1386084

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism2017

    • Author(s)
      Xu Minjun、Kitaura Yasuyuki、Ishikawa Takuya、Kadota Yoshihiro、Terai Chihaya、Shindo Daichi、Morioka Takashi、Ota Miki、Morishita Yukako、Ishihara Kengo、Shimomura Yoshiharu
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0180989-e0180989

    • DOI

      10.1371/journal.pone.0180989

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.2017

    • Author(s)
      Honda T, Ishigami M, Luo F, Lingyun M, Ishizu Y, Kuzuya T, Hayashi K, Nakano I, Ishikawa T, Feng GG, Katano Y, Kohama T, Kitaura Y, Shimomura Y, Goto H, Hirooka Y.
    • Journal Title

      Metabolism

      Volume: 69 Pages: 177-187

    • DOI

      10.1016/j.metabol.2016.12.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 脂肪組織の分岐鎖アミノ酸(BCAA)欠乏による耐糖能への影響2019

    • Author(s)
      千田壮志、加賀清美、北浦靖之、下村吉治
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 運動持久力に対する筋特異的分岐鎖アミノ酸(BCAA)分解亢進の影響:筋グリコーゲン代謝とBCAA2019

    • Author(s)
      山田みのり、北浦靖之、水澤杏南、山田靖子、鈴木竜成、佐野仁志、下村吉治
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effect of genetically decreased BCAA concentration on glucose tolerance in mice2019

    • Author(s)
      Y. Kitaura, S. Senda, Y. Shimomura
    • Organizer
      13th Asian Congress of Nutrition (ACN) 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 前頭部興奮性ニューロン特異的BDK欠損マウスの特徴解析2019

    • Author(s)
      水澤杏南、山田みのり、下村吉治、北浦靖之
    • Organizer
      日本アミノ酸学会第13回学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 筋グリコーゲン代謝に対する分岐鎖アミノ酸(BCAA)の影響2019

    • Author(s)
      山田みのり、水澤杏南、北浦靖之、下村吉治
    • Organizer
      日本アミノ酸学会第13回学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The roles of branched-chain amino acids (BCAAs) in regulation of muscle protein metabolism and physical activity2019

    • Author(s)
      Y. Shimomura, Y. Kitaura
    • Organizer
      7th International Conference on Food Factors (ICoFF) Symposium 55 "Skeletal Muscle Health"
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 筋グリコーゲン量に対する筋特異的分岐鎖アミノ酸(BCAA)分解亢進の影響2019

    • Author(s)
      山田 みのり, 北浦 靖之, 下村 吉治
    • Organizer
      第23回日本体力医学会東海地方会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 必須アミノ酸摂取による骨格筋機能改善:分岐鎖アミノ酸(BCAA)の作用を中心として2018

    • Author(s)
      下村 吉治, 北浦 靖之
    • Organizer
      第55回日本臨床生理学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脂肪組織における分岐鎖アミノ酸の欠乏は耐糖能悪化を助長する2018

    • Author(s)
      千田 壮志, 加賀 清美, 北浦 靖之, 下村 吉治
    • Organizer
      日本アミノ酸学会第12回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋グリコーゲン量に対する筋特異的分岐鎖アミノ酸分解亢進の影響2018

    • Author(s)
      山田 みのり, 北浦 靖之, 水澤 杏南, 山田 靖子, 鈴木 竜成, 佐野 仁志, 下村 吉治
    • Organizer
      日本アミノ酸学会第12回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分岐アミノ酸の代謝と生理機能2018

    • Author(s)
      下村 吉治
    • Organizer
      日本アミノ酸学会第12回学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Diversity of Physiological Functions of Branched-chain Amino Acids (BCAAs)2018

    • Author(s)
      Shimomura Y, Kitaura Y.
    • Organizer
      ISTRY2018(第15回国際トリプトファン学会)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Calcium ion enhances inhibition of the BCKDH kinase by thiamine pyrophosphate (TPP)2018

    • Author(s)
      Yoshiharu Shimomura, Seisuke Noguchi, Yasuyuki Kitaura
    • Organizer
      NUTRITION 2018(米国栄養学会)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウスの脂肪蓄積に対するBCAA代謝亢進の影響2018

    • Author(s)
      加賀 清美, 門田 吉弘, Jussiaea Bariuan, 千田 壮志, 北浦 靖之, 下村 吉治
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨格筋タンパク質合成に対する筋特異的BCAA代謝亢進と低タンパク質食摂取の影響2018

    • Author(s)
      山田 靖子, 山中 郁弥, 佐野 仁志, 北浦 靖之, 下村 吉治
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分岐鎖アミノ酸の生理機能の多様性2018

    • Author(s)
      下村吉治
    • Organizer
      第15回レドックス・ライフイノベーション シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] マウスのエネルギー代謝に対する脂肪組織特異的分岐鎖アミノ酸代謝の影響2017

    • Author(s)
      加賀 清美, Jussiaea Bariuan, 千田 壮志, 北浦 靖之, 下村 吉治
    • Organizer
      第73回日本栄養・食糧学会中部支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Diverse functions of branched-chain amino acid (BCAAs)2017

    • Author(s)
      Yoshiharu Shimomura
    • Organizer
      2017 The Korean Nutrition Society 50th Anniversary International Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Sports Nutrition for an active life-style.2017

    • Author(s)
      Yoshiharu Shimomura
    • Organizer
      IUNS 21st International Congress of Nutrition, Symposium144/1028
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] BCAA代謝を調節するビタミンB12017

    • Author(s)
      下村吉治
    • Organizer
      日本ビタミン学会第69回大会シンポジウム「アミノ酸代謝を調節する補因子研究の最前線」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Adaptability to exercise training and energy metabolism during exercise in mice with muscle-specific deletion of BDK.2017

    • Author(s)
      Yoshiharu Shimomura
    • Organizer
      Emerging role of Branched-chain Amino Acids in human diseases
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ca2+による分岐鎖アミノ酸代謝の調節2017

    • Author(s)
      野口 晴右, 伊藤 里奈, 近藤 雄介, 北浦 靖之, 下村 吉治
    • Organizer
      第71回日本栄養・食糧学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 恒常的な筋特異的BCAA 分解亢進による筋タンパク質代謝の変化2017

    • Author(s)
      山中 郁弥, 石川 卓弥, 森下 由佳子, 山田 靖子, 北浦 靖之, 下村 吉治
    • Organizer
      第71回日本栄養・食糧学会大会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-23  

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