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Epigenetic mechanisms of metabolic reprogramming under nutritional stress

Research Project

Project/Area Number 16K07215
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical genome science
Research InstitutionKumamoto University

Principal Investigator

Hino Shinjiro  熊本大学, 発生医学研究所, 准教授 (00448523)

Research Collaborator ANAN Kotaro  
TAKASE Ryuta  
KOHROGI Kensaku  
ARAKI Hirotaka  
HINO Yuko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsヒストン脱メチル化 / 代謝リプログラミング / 筋線維型 / 骨格筋 / 線維型 / LSD1 / グルココルチコイド / クロマチン / エネルギー代謝 / ゲノム / エピジェネティクス
Outline of Final Research Achievements

Skeletal muscle is composed of two different fiber types, fast- and slow-twitch fibers. While the fast is specialized for dynamic movements and glycolytic metabolism, the slow is specialized for endurance and show active mitochondrial respiration. Composition of these fiber types is highly influenced by environmental factors such as exercise and diet, and is associated with the risks of chronic diseases such as diabetes. This study was aimed at elucidating the mechanisms by which fiber types are determined under the influence of environmental factors. We found that a histone demethylase, LSD1, represses both slow fiber and respiration associated genes to promote fast fiber traits. In addition, we found that glucocorticoid, a hormone secreted in undernutrition state, promotes the degradation of LSD1 leading to the enhanced slow fiber formation. Our findings uncover the molecular mechanisms that link environment to muscle fiber, and would contribute to understanding chronic diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究により、骨格筋の機械的性質とエネルギー代謝特性を連動させる遺伝子発現調節機構が明らかとなった。また、栄養環境が長期的な筋線維組成に反映される仕組みが明らかになった。これらの成果は、環境によって動物の体質が可塑的に変化する仕組みを理解する上で大きな手掛かりとなる。また、生活習慣病などの慢性疾患の発症機序解明に貢献できると考えられ、予防法や治療法の開発に資する。

Report

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

    (39 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 9 results,  Acknowledgement Compliant: 3 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Texas/Novartis Institutes(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Koln(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Texas/Novartis Institutes(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Lysine-specific demethylase-2 is distinctively involved in brown and beige adipogenic differentiation2019

    • Author(s)
      Takase Ryuta、Hino Shinjiro、Nagaoka Katsuya、Anan Kotaro、Kohrogi Kensaku、Araki Hirotaka、Hino Yuko、Sakamoto Akihisa、Nicholson Thomas B.、Chen Taiping、Nakao Mitsuyoshi
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 4 Pages: 5300-5311

    • DOI

      10.1096/fj.201801422rr

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.2019

    • Author(s)
      Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G.
    • Journal Title

      Commun. Biol.

      Volume: eCollection Issue: 1 Pages: 95-95

    • DOI

      10.1038/s42003-019-0336-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ヒストン脱メチル化酵素LSD1による骨格筋細胞の代謝リプログラミング2019

    • Author(s)
      阿南 浩太郎、日野 信次朗、中尾 光善
    • Journal Title

      生化学

      Volume: 91 Pages: 31-37

    • Related Report
      2018 Annual Research Report
  • [Journal Article] LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation2018

    • Author(s)
      K. Anan, S. Hino, N. Shimizu, A. Sakamoto, K. Nagaoka, R. Takase, K. Kohrogi, H. Araki, Y. Hino, S. Usuki, S. Oki, H. Tanaka, K. Nakamura, F. Endo, and M. Nakao
    • Journal Title

      Nucleic Acids Res.

      Volume: 18 Issue: 11 Pages: 5441-5454

    • DOI

      10.1093/nar/gky234

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal undernutrition during early pregnancy inhibits postnatal growth of the tibia in the female offspring of rats by alteration of chondrogenesis2018

    • Author(s)
      Kimura Tomoko、Hino Kodai、Kono Tadaaki、Takano Atsushi、Nitta Norihisa、Ushio Noritoshi、Hino Shinjiro、Takase Ryuta、Kudo Motoi、Daigo Yataro、Morita Wataru、Nakao Mitsuyoshi、Nakatsukasa Masato、Tamagawa Toshihiro、Rafiq Ashiq Mahmood、Matsumoto Akihiro、Otani Hiroki、Udagawa Jun
    • Journal Title

      General and Comparative Endocrinology

      Volume: 260 Issue: 1 Pages: 58-66

    • DOI

      10.1016/j.ygcen.2017.12.008

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 食事はメモリーされる:栄養・代謝とエピゲノム2017

    • Author(s)
      荒木裕貴、日野信次朗、中尾光善
    • Journal Title

      Diabetes Frontier

      Volume: 28 Pages: 617-621

    • Related Report
      2017 Research-status Report
  • [Journal Article] 肝糖代謝とヒストンメチル化修飾2017

    • Author(s)
      日野信次朗
    • Journal Title

      肝胆膵

      Volume: 75 Pages: 11-15

    • Related Report
      2017 Research-status Report
  • [Journal Article] エネルギー代謝のエピジェネティクス2017

    • Author(s)
      日野信次朗
    • Journal Title

      最新医学

      Volume: 72 Pages: 672-677

    • Related Report
      2017 Research-status Report
  • [Journal Article] The SETD8/PR-Set7 Methyltransferase Functions as a Barrier to Prevent Senescence-Associated Metabolic Remodeling.2017

    • Author(s)
      Tanaka, H., Takebayashi S. I., Sakamoto, A., Igata, T., Nakatsu, Y., Saitoh, N., Hino, S., and Nakao, M.
    • Journal Title

      Cell Rep.

      Volume: 18 Issue: 9 Pages: 2148-2161

    • DOI

      10.1016/j.celrep.2017.02.021

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The glucocorticoid receptor regulates the ANGPTL4 gene in a CTCF-mediated chromatin context in human hepatic cells2017

    • Author(s)
      M. Nakamoto, K. Ishihara, T. Watanabe, A. Hirosue, S. Hino, M. Shinohara, H. Nakayama, and M. Nakao.
    • Journal Title

      PLoS One

      Volume: 12 Issue: 1 Pages: e0169225-e0169225

    • DOI

      10.1371/journal.pone.0169225

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38 MAPK-gamma activity2016

    • Author(s)
      T. Tsutsumi, K. Iwao, H. Hayashi, T. Kawaji, T. Inoue, S. Hino, M. Nakao, and H. Tanihara.
    • Journal Title

      Invest. Ophthalmol. Vis. Sci.

      Volume: 57 Issue: 14 Pages: 6461-6473

    • DOI

      10.1167/iovs.16-19494

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells2016

    • Author(s)
      S. Hino, K. Kohrogi, and M. Nakao.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 9 Pages: 1187-1192

    • DOI

      10.1111/cas.13004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Application of targeted enrichment to next-generation sequencing of retroviruses integrated into the host human genome.2016

    • Author(s)
      Miyazato P, Katsuya H, Fukuda A, Uchiyama Y, Matsuo M, Tokunaga M, Hino S, Nakao M, and Satou Y*.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 28324-28324

    • DOI

      10.1038/srep28324

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] FAD依存性ヒストン脱メチル化酵素による遺伝子制御2016

    • Author(s)
      日野信次朗、阿南浩太郎、高瀬隆太、興梠健作、中尾光善
    • Journal Title

      実験医学

      Volume: 34 Pages: 2486-2492

    • Related Report
      2016 Research-status Report
  • [Journal Article] 環境エピゲノムとヒトの疾患2016

    • Author(s)
      興梠健作、日野信次朗、中尾光善
    • Journal Title

      BIO Clinica

      Volume: 31 Pages: 455-459

    • Related Report
      2016 Research-status Report
  • [Presentation] Hormone-Responsive Epigenetic Mechanisms Underlying Metabolic Reprogramming in the Muscle.2018

    • Author(s)
      Hino S.
    • Organizer
      The 14th International Symposium on Geriatrics and Gerontology Bridging Dementia and Frailty ~ From Pathogenesis to Prevention~
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] フラビン依存性ヒストン脱メチル化酵素によるエネルギー代謝制御2018

    • Author(s)
      日野信次朗
    • Organizer
      産総研バイオメディカル研究部門セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] LSD1による白血病細胞系譜に応じた代謝制御機構2018

    • Author(s)
      日野信次朗、興梠健作、阿南浩太郎、高瀬隆太、荒木裕貴、中尾光善
    • Organizer
      第12回日本エピジェネティクス研究会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フラビン依存性ヒストン脱メチル化酵素によるエネルギー代謝制御2018

    • Author(s)
      日野信次朗
    • Organizer
      熊本大学血液内科カンファレンス
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] フラビン依存性脱メチル化酵素によるエピゲノム制御と代謝疾患2018

    • Author(s)
      日野信次朗
    • Organizer
      第55回日本臨床分子医学会学術集会(スポンサーセミナー:細胞増殖を取り巻く多彩な生命現象 -免疫、代謝、脂質、エピゲノム-)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Epigenetic control of white and brown adipogenesis by a histone demethylase, LSD2.2018

    • Author(s)
      Takase R., Hino S., Nagaoka K., Anan K., Kohrogi K., Araki H. and Nakao M.
    • Organizer
      JSPS and NUS Joint 2nd Symposium.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 代謝-エピゲノムクロストークの分子機構2018

    • Author(s)
      日野信次朗
    • Organizer
      第1回がんと代謝研究会 若手の会
    • Related Report
      2017 Research-status Report
  • [Presentation] FAD依存性ヒストン脱メチル化酵素によるエネルギー代謝制御機構2017

    • Author(s)
      日野信次朗
    • Organizer
      第302回熊本大学発生研セミナー
    • Place of Presentation
      熊本市 熊本大学発生医学研究所
    • Year and Date
      2017-02-21
    • Related Report
      2016 Research-status Report
  • [Presentation] FAD依存性ヒストン脱メチル化酵素によるエネルギー代謝制御機構2017

    • Author(s)
      日野信次朗
    • Organizer
      東京大学医科学研究所学友会セミナー
    • Place of Presentation
      東京都港区 東京大学医科学研究所
    • Year and Date
      2017-01-16
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] ヒストン脱メチル化酵素LSD1による酸素環境応答と代謝可塑性2017

    • Author(s)
      日野信次朗、阿南浩太郎、高瀬隆太、興梠健作、中尾光善
    • Organizer
      ConBio2017(ワークショップ:分子状酸素による遺伝子発現調節から紐解く疾患生物学)
    • Related Report
      2017 Research-status Report
  • [Presentation] 環境に応じた代謝可塑性を司るエピジェネティクス機構2017

    • Author(s)
      日野信次朗
    • Organizer
      山口大学大学院連合獣医学研究科 大学院生企画セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] LSD1による代謝調節とがん2017

    • Author(s)
      日野信次朗
    • Organizer
      第5回がんと代謝研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] ホルモン応答性エピゲノム制御による骨格筋代謝制御機構2017

    • Author(s)
      日野信次朗、阿南浩太郎、高瀬隆太、興梠健作、中尾光善
    • Organizer
      第90回日本内分泌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒストン脱メチル化酵素LSD1を介した環境応答と細胞記憶の形成2016

    • Author(s)
      日野信次朗
    • Organizer
      第39回日本分子生物学会年会(フォーラム:マルチオミクス統合解析が解き明かす生命現象-発生から疾患まで-)
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Regulation of cellular metabolism by histone demethylase LSD12016

    • Author(s)
      Hino S.
    • Organizer
      The 12th Japan-China Cooperative Life Science Symposium
    • Place of Presentation
      Kumamoto University, Kumamoto
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of cellular metabolism by histone demethylase LSD12016

    • Author(s)
      Hino S.
    • Organizer
      The 26th Hot Spring Harbor International Symposium
    • Place of Presentation
      Kyushu University, Fukuoka
    • Year and Date
      2016-11-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 所属研究所ウェブサイト

    • URL

      http://www.imeg.kumamoto-u.ac.jp

    • Related Report
      2018 Annual Research Report
  • [Remarks] 熊本大学発生医学研究所ホームページ

    • URL

      http://www.imeg.kumamoto-u.ac.jp/

    • Related Report
      2017 Research-status Report
  • [Remarks] 研究成果のプレス発表

    • URL

      http://www.kumamoto-u.ac.jp/whatsnew/seimei/20180330

    • Related Report
      2017 Research-status Report
  • [Remarks] 熊本大学発生医学研究所ホームページ

    • URL

      http://www.imeg.kumamoto-u.ac.jp

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 浮遊性細胞のリアルタイム測定トレイと測定装置、ならびにそれを用い   た測定方法2018

    • Inventor(s)
      中尾光善、日野信次朗、興梠健作、岩佐卓哉、熊谷聡士
    • Industrial Property Rights Holder
      中尾光善、日野信次朗、興梠健作、岩佐卓哉、熊谷聡士
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2022-02-21  

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