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Epigenetic modofication of neuronal nitric oxide synthase gene in skeletal muscle on glucose metabolism

Research Project

Project/Area Number 15H03082
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Sports science
Research InstitutionFukuoka University

Principal Investigator

Higaki Yasuki  福岡大学, スポーツ科学部, 教授 (10228702)

Co-Investigator(Kenkyū-buntansha) 田中 宏暁  福岡大学, スポーツ科学部, 非常勤講師 (00078544)
須藤 みず紀  公益財団法人明治安田厚生事業団体力医学研究所, その他部局等, 研究員(移行) (10585186)
道下 竜馬  福岡大学, スポーツ科学部, 准教授 (10632028)
安藤 創一  電気通信大学, 大学院情報理工学研究科, 准教授 (50535630)
上原 吉就  福岡大学, スポーツ科学部, 教授 (70373149)
安野 哲彦  福岡大学, 医学部, 講師 (80551994)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
KeywordsDNAメチル化 / 一酸化窒素合成酵素 / 運動適応 / エピジェネティクス / 高脂肪食 / 腎機能低下 / エピゲノム / メチル化
Outline of Final Research Achievements

We determined whether neuronal nitric oxide synthase (nNOS) DNA methylation is involved in the regulation in gene expression in mice skeletal muscle and brain under physical inactivity, aging, and exercise training. The average nNOS DNA methylation level in skeletal muscle after cast immobilization was significantly increased compared with that in control mice, suggesting epigenetic modification occurred in inactive muscle. We also determined the association between ageing and nNOS expression in the brain from rearing mice in an enriched environment (EE) or sedentary environment. We observed that nNOS expression levels increased with age in the brain aged mice. While EE reduced nNOS expression in the brain. In the present state we did not clear the association nNOS gene expression and DNA methylation in the brain. Our studies suggest that physical activity has therapeutic potential to prevent muscle atrophy and age-related impairment of brain function via nNOS/NO pathway.

Academic Significance and Societal Importance of the Research Achievements

身体不活動や肥満による生活習慣病の蔓延は、医療費の増大を招くことから、早急に対策を講じる必要のある喫緊の課題である。しかしながら、なぜ、身体不活動や肥満が、糖尿病や認知症などに代表される生活習慣病を惹起するのかその詳細なメカニズムはわかっていなかった。本研究では、骨格筋の糖代謝調節の一端を担う一酸化窒素に着目し、その合成酵素である神経型一酸化窒素合成酵素の遺伝子発現が、DNAのメチル化を介して調節されている可能性を明らかにした。一酸化窒素は、筋萎縮や加齢による不安現象と関係していることがわかっており、将来的にはサルコペニア・フレイル予防や認知症予防につながる研究となることを期待している。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (22 results)

All 2019 2018 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Long-term Body Weight Gain After Maturity is Associated With the Incidence of Chronic Kidney Disease (CKD), Independent of Current Body Weight, in Middle-aged and Older Men2019

    • Author(s)
      Michishita Ryoma、Matsuda Takuro、Kawakami Shotaro、Tanaka Satoshi、Kiyonaga Akira、Tanaka Hiroaki、Morito Natsumi、Higaki Yasuki
    • Journal Title

      Journal of Epidemiology

      Volume: 29 Issue: 6 Pages: 213-219

    • DOI

      10.2188/jea.JE20170304

    • NAID

      130007659760

    • ISSN
      0917-5040, 1349-9092
    • Year and Date
      2019-06-05
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effect of exercise intensity on renal blood flow in patients with chronic kidney disease stage 2.2019

    • Author(s)
      Kotoku K, Yasuno T, Kawakami S, Fujimi K, Matsuda T, Nakashima S, Uehara Y, Tanaka H, Saito T, Higaki Y
    • Journal Title

      Clin Exp Nephrol

      Volume: 印刷中 Issue: 5 Pages: 621-628

    • DOI

      10.1007/s10157-018-01685-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Short- and long-term effects of high-fat diet feeding and voluntary exercise on hepatic lipid metabolism in mice.2018

    • Author(s)
      Yoshimura S, Nakashima S, Tomiga Y, Kawakami S, Uehara Y, Higaki Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 507 Issue: 1-4 Pages: 291-296

    • DOI

      10.1016/j.bbrc.2018.11.026

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 慢性腎臓病(CKD)発症予防に対する生活習慣2018

    • Author(s)
      道下竜馬、森戸夏美、田中宏暁、檜垣靖樹
    • Journal Title

      日本臨床生理学雑誌

      Volume: 48(5) Pages: 147-153

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exercise training rescues high fat diet-induced neuronal nitric oxide synthase expression in the hippocampus and cerebral cortex of mice2017

    • Author(s)
      Tomiga Yuki、Yoshimura Saki、Ito Ai、Nakashima Shihoko、Kawanaka Kentaro、Uehara Yoshinari、Tanaka Hiroaki、Higaki Yasuki
    • Journal Title

      Nitric Oxide

      Volume: 66 Pages: 71-77

    • DOI

      10.1016/j.niox.2017.03.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of environmental enrichment in aged mice on anxiety-like behaviors and neuronal nitric oxide synthase expression in the brain2016

    • Author(s)
      Yuki Tomiga, Ai Ito, Mizuki Sudo, Soichi Ando, Akino Maruyama, Shihoko Nakashima, Kentaro Kawanaka, Yoshinari Uehara, Akira Kiyonaga, Hiroaki Tanaka, Yasuki Higaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 476 Issue: 4 Pages: 635-640

    • DOI

      10.1016/j.bbrc.2016.06.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 高脂肪食誘発性脂肪肝に対する運動効果は短期間でも認められるか2018

    • Author(s)
      吉村咲紀他
    • Organizer
      日本体力医学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高脂肪食誘発性脂肪肝に対する自発運動の効果―経時的な変化に着目して―2018

    • Author(s)
      吉村咲紀他
    • Organizer
      日本肥満学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 加齢性及び廃用性萎縮骨格筋におけるnNOSのDNAメチル化パターンの違い2018

    • Author(s)
      冨賀裕貴他
    • Organizer
      日本体力医学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of exercise intensity on autoregulation of GFR in patients with chronic kidney disease stage 22018

    • Author(s)
      Kotoku K et al.
    • Organizer
      アメリカ腎臓病学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎血流量を減少させない安全な運動強度2017

    • Author(s)
      檜垣靖樹
    • Organizer
      第17回日本糖尿病情報学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高脂肪食摂取及び自発的運動がもたらす肝臓脂肪分布の変化2017

    • Author(s)
      吉村咲紀, 冨賀裕貴, 釘本郁美, 後藤里奈, 中島志穂子, 田中宏暁, 上原吉就, 檜垣靖樹
    • Organizer
      九州体育・スポーツ学会第66回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Time-course effects of exercise on anxiety-like behaviors andhippocampal neuronal nitric oxide synthase in high fat diet-induced obese mice2017

    • Author(s)
      Tomiga Y, Yoshimura S, Takahashi Y, Goto R, Kugimoto I, Uehara Y, Kawanaka K, Tanaka H, Higaki Y
    • Organizer
      Cell symposia Exercise metabolism
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exercise training rescues high fat diet-induced neuronal nitric oxide synthase expression in hippocampus and cortex2017

    • Author(s)
      Tomiga Y, Yoshimura S, Ito A, Kawanaka K, Uehara Y, Tanaka H, Higaki Y
    • Organizer
      The 64nd American College of Sports Medicine Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fat accumulation processes in the liver of trained mice and untraine2017

    • Author(s)
      S. Yoshimura*, Y. Tomiga, S. Nakashima, R. Goto, I. Kugimoto, Y. Takahashi, Y. Uehara, Y. Higaki
    • Organizer
      Cell symposia Exercise metabolism
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association between anxiety-like behaviors and neuronal nitric oxide synthase in old mice under enriched environment2016

    • Author(s)
      Yuki Tomiga, Ai Ito, Akino Maruyama, Mizuki Sudo, Soichi Ando, Kentaro Kawanaka, Hiroaki Tanaka, Yasuki Higaki
    • Organizer
      The 2016 American College of Sports Medicine
    • Place of Presentation
      Boston
    • Year and Date
      2016-05-31
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association between anziety-like behaviors and neuronal nitric oxide synthase in old mice under enriched environment2016

    • Author(s)
      Tomiga Y, Ito A, Maruyama A, Sudo M, Ando S, Kawanaka K, Tanaka H, Higaki Y
    • Organizer
      ACSM's 63rd annual meeting
    • Place of Presentation
      Boston
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of wheel running exercise training in high fat diet induced fatty liver model mice2016

    • Author(s)
      Yoshimura S, Nakashima S, Tomiga Y, Ito A, Kawakami S, Tanaka H, Uehara Y, Higaki Y
    • Organizer
      第71回日本体力医学会大会
    • Place of Presentation
      盛岡市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effects of a high fat diet and exercise on glycogen contents2016

    • Author(s)
      Kugimoto I, Yoshimura S, Tomiga Y, Nakashima S, Uehara Y, TanakaH, Higaki Y
    • Organizer
      第71回日本体力医学会大会
    • Place of Presentation
      盛岡市
    • Related Report
      2016 Annual Research Report
  • [Presentation] The effects of high fat diet-induced obesity and exercise training on neuronal nitric oxide synthase expression and DNA methylation levels in skeletal muscle.2016

    • Author(s)
      TomigaY, Yoshimura S, Ito A, Sudo M, Ando S, Eshima H, Tanaka H, Higaki Y
    • Organizer
      第71回日本体力医学会大会
    • Place of Presentation
      盛岡市
    • Related Report
      2016 Annual Research Report
  • [Presentation] 組織及び筋線維タイプにおけるnNOSのDNAメチル化修飾に関する研究2015

    • Author(s)
      伊藤 愛, 冨賀 裕貴, 須藤 みず紀, 安藤 創一, 中島 志穂子, 田中 宏暁, 檜垣 靖樹
    • Organizer
      日本体力医学会大会
    • Place of Presentation
      和歌山県
    • Year and Date
      2015-09-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 片脚ギプス固定による筋萎縮がnNOSプロモーター領域のDNAメチル化修飾に及ぼす影響2015

    • Author(s)
      冨賀 裕貴, 伊藤 愛, 須藤 みず紀, 安藤 創一, 中島 志穂子, 田中 宏暁, 檜垣 靖樹
    • Organizer
      日本体力医学会大会
    • Place of Presentation
      和歌山県
    • Year and Date
      2015-09-18
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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