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Molecular mechanisms underlying sarcopenia and its associated obesity

Research Project

Project/Area Number 19H04058
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
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) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsサルコペニア / 肥満 / 骨格筋 / 遺伝子発現 / 食品成分 / 筋萎縮 / エネルギー消費 / 転写調節因子 / 運動
Outline of Research at the Start

サルコペニア(加齢や不活動・低栄養・疾患などによる筋萎縮・筋機能低下)とそれに伴う肥満(サルコペニア肥満)は超高齢社会の我が国で直面している問題である。本研究では、独自に作製した遺伝子改変マウス等のオミクス解析、転写調節因子の活性を指標とした食品成分のスクリーニング、筋初代培養など細胞を用いたin vitroの分子生物学的解析を組み合わせ、サルコペニアとサルコペニア肥満の発症と予防・改善の分子基盤を解明する。本研究課題の遂行により、超高齢社会の健康寿命延伸の手がかりとなり、また骨格筋を主体とした生理・病態生理現象の解明により健康科学分野進展への波及効果が期待される。

Outline of Final Research Achievements

Our aim has been to better understand the molecular mechanisms underlying sarcopenia and associated obesity. Based on our previous data, we have been focusing on FOXO1, PGC1 and Dnmt3a, which are transcriptional regulators. We performed omics analysis using gene- modified mice, and conducted a screening of food components, as well as in vitro molecular biological analysis. We found that soy isoflavones activated fat-usage genes (soy isoflavone is likely to attenuate obesity), and vitamin D suppressed atrophy genes in the skeletal muscle (vitamin D is a potential inhibitor of muscle atrophy). We identified numerous target genes, which are regulated during atrophy and exercise. By further analysis, the mechanisms related to sarcopenia, the prevention of atrophy and improvement of exercise capability, will be clarified, and knowledge on functional foods will be obtained.

Academic Significance and Societal Importance of the Research Achievements

サルコペニア(加齢や不活動・低栄養・疾患などによる筋萎縮・筋機能低下)とそれに伴う肥満(サルコペニア肥満)は超高齢社会の我が国で直面している問題である。本研究の実施により、サルコペニアとサルコペニア肥満の発症と予防・改善の分子基盤の手がかりを得た。本研究の成果を発展させることにより、超高齢社会の健康寿命延伸の手がかりとなり、また骨格筋を主体とした生理・病態生理現象の解明による健康科学分野進展への波及効果が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (47 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (17 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 17 results,  Open Access: 16 results) Presentation (24 results) (of which Int'l Joint Research: 7 results,  Invited: 14 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] University of Camerino(イタリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Miami Miller(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Vitamin D Activates Various Gene Expressions, Including Lipid Metabolism, in C2C12 Cells2022

    • Author(s)
      MIZUTANI Sako、OYABU Mamoru、YAMAMOTO Arisa、UCHITOMI Ran、SUGIMOTO Takumi、KAMEI Yasutomi
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 68 Issue: 1 Pages: 65-72

    • DOI

      10.3177/jnsv.68.65

    • NAID

      130008164781

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2022-02-28
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FOXO1 cooperates with C/EBPδ and ATF4 to regulate skeletal muscle atrophy transcriptional program during fasting2022

    • Author(s)
      Oyabu Mamoru、Takigawa Kaho、Mizutani Sako、Hatazawa Yukino、Fujita Mariko、Ohira Yuto、Sugimoto Takumi、Suzuki Osamu、Tsuchiya Kyoichiro、Suganami Takayoshi、Ogawa Yoshihiro、Ishihara Kengo、Miura Shinji、Kamei Yasutomi
    • Journal Title

      The FASEB Journal

      Volume: 36 Issue: 2

    • DOI

      10.1096/fj.202101385rr

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The endothelial Dll4?muscular Notch2 axis regulates skeletal muscle mass2022

    • Author(s)
      Fujimaki Shin、Matsumoto Tomohiro、Muramatsu Masashi、Nagahisa Hiroshi、Horii Naoki、Seko Daiki、Masuda Shinya、Wang Xuerui、Asakura Yoko、Takahashi Yukie、Miyamoto Yuta、Usuki Shingo、Yasunaga Kei-ichiro、Kamei Yasutomi、Nishinakamura Ryuichi、Minami Takashi、Fukuda Takaichi、Asakura Atsushi、Ono Yusuke
    • Journal Title

      Nature Metabolism

      Volume: 4 Issue: 2 Pages: 180-189

    • DOI

      10.1038/s42255-022-00533-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolomic analysis on blood of transgenic mice overexpressing PGC-1α in skeletal muscle2021

    • Author(s)
      Sugimoto Takumi、Uchitomi Ran、Hatazawa Yukino、Miura Shinji、Kamei Yasutomi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 85 Issue: 3 Pages: 579-586

    • DOI

      10.1093/bbb/zbaa059

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle.2021

    • Author(s)
      Yoshioka K, Nagahisa H, Miura F, Araki H, Kamei Y, Kitajima Y, Seko D, Nogami J, Tsuchiya Y, Okazaki N, Yonekura A, Ohba S, Sumita Y, Chiba K, Ito K, Asahina I, Ogawa Y, Ito T, Ohkawa Y, Ono Y.
    • Journal Title

      Sci Adv.

      Volume: 7 Issue: 24

    • DOI

      10.1126/sciadv.abd7924

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Citrus hassaku Extract Powder Increases Mitochondrial Content and Oxidative Muscle Fibers by Upregulation of PGC-1α in Skeletal Muscle2021

    • Author(s)
      Akashi Shiori、Morita Akihito、Mochizuki Yusuke、Shibuya Fuka、Kamei Yasutomi、Miura Shinji
    • Journal Title

      Nutrients

      Volume: 13 Issue: 2 Pages: 497-497

    • DOI

      10.3390/nu13020497

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Skeletal muscle-specific forkhead box protein-O1 overexpression suppresses atherosclerosis progression in apolipoprotein E-knockout mice2021

    • Author(s)
      Shimba Yuki、Senda Rena、Katayama Keigo、Morita Akihito、Ikeda Masahiko、Kamei Yasutomi、Miura Shinji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 540 Pages: 61-66

    • DOI

      10.1016/j.bbrc.2021.01.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of fenofibrate and its combination with lovastatin on the expression of genes involved in skeletal muscle atrophy, including FoxO1 and its targets2021

    • Author(s)
      Ajima Haruka、Kai Yuko、Fujimaki Junya、Akashi Shiori、Morita Akihito、Ezaki Osamu、Kamei Yasutomi、Miura Shinji
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 46 Issue: 1 Pages: 11-24

    • DOI

      10.2131/jts.46.11

    • NAID

      130007966022

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Health Promotion Effects of Soy Isoflavones2020

    • Author(s)
      NAKAI Shiho、FUJITA Mariko、KAMEI Yasutomi
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 66 Issue: 6 Pages: 502-507

    • DOI

      10.3177/jnsv.66.502

    • NAID

      130007964468

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2020-12-31
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitamin D and Sarcopenia: Potential of Vitamin D Supplementation in Sarcopenia Prevention and Treatment2020

    • Author(s)
      Uchitomi Ran、Oyabu Mamoru、Kamei Yasutomi
    • Journal Title

      Nutrients

      Volume: 12 Issue: 10 Pages: 3189-3189

    • DOI

      10.3390/nu12103189

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FOXO1 suppresses PGC‐1β gene expression in skeletal muscles2020

    • Author(s)
      Nakai Shiho、Oyabu Mamoru、Hatazawa Yukino、Akashi Shiori、Kitamura Tadahiro、Miura Shinji、Kamei Yasutomi
    • Journal Title

      FEBS Open Bio

      Volume: 10 Issue: 7 Pages: 1373-1388

    • DOI

      10.1002/2211-5463.12898

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Skeletal Muscle Function by Amino Acids2020

    • Author(s)
      Kamei Yasutomi、Hatazawa Yukino、Uchitomi Ran、Yoshimura Ryoji、Miura Shinji
    • Journal Title

      Nutrients

      Volume: 12 Issue: 1 Pages: 261-261

    • DOI

      10.3390/nu12010261

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening dataset of food components that enhance transcriptional activity of PGC1-beta2019

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

      Data in Brief

      Volume: 23 Pages: 103814-103814

    • DOI

      10.1016/j.dib.2019.103814

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolomic analysis of skeletal muscle in aged mice.2019

    • Author(s)
      Uchitomi, R., Hatazawa, Y., Senoo, N., Yoshioka, K., Fujita, M., Shimizu, T., Miura, S., Ono, Y., and Kamei, Y.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 10425-10425

    • DOI

      10.1038/s41598-019-46929-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO 12019

    • Author(s)
      Matsuda Rintaro、Uchitomi Ran、Oyabu Mamoru、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      FEBS Letters

      Volume: 593 Issue: 12 Pages: 1303-1312

    • DOI

      10.1002/1873-3468.13445

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [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
      2019 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
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] FOXO1はマウス骨格筋エネルギー代謝に重要なPGC-1βの遺伝子発現を負に制御する2021

    • Author(s)
      亀井康富、中井志帆、大藪葵、畑澤幸乃、明石汐里、三浦進司
    • Organizer
      日本肥満学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨格筋機能とアミノ酸2021

    • Author(s)
      亀井康富
    • Organizer
      日本アミノ酸学会第15回学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 骨格筋と栄養2021

    • Author(s)
      亀井康富
    • Organizer
      日本栄養食糧学会 第60回近畿支部大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Gene expression analysis in skeletal muscle cells supplemented with vitamin D2021

    • Author(s)
      Mizutani Sako, Oyabu Mamoru, Yamamoto Arisa, Sugimoto Takumi, Kamei Yasutomi
    • Organizer
      Keystone symposium, Vitamin D Workshop
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the mechanism of differentiation from muscle satellite cells into fast muscle fibers and involvement of Vitamin D2021

    • Author(s)
      Yuto Ohira, Mariko Fujita, Kaho Takigawa, Kiyoshi Yoshioka, Yusuke Ono, Yasutomi Kamei
    • Organizer
      Keystone symposium, Vitamin D Workshop
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 転写因子FOXO1は骨格筋エネルギー代謝に重要な転写調節因子PGC-1βの発現を抑制する2020

    • Author(s)
      亀井康富、中井志帆、大藪葵、畑澤幸乃
    • Organizer
      第74回 日本栄養・食糧学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生活習慣病予防における骨格筋の役割2020

    • Author(s)
      亀井康富
    • Organizer
      NPO法人近畿バイオインダストリー振興会議 第3回 生活習慣病予防のための機能性食品開発に関する研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ビタミンDとサルコペニア2020

    • Author(s)
      亀井康富
    • Organizer
      神戸女子大学栄養研究会主催講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 骨格筋萎縮における代謝産物と遺伝子発現の変化2020

    • Author(s)
      亀井康富
    • Organizer
      日本分子生物学会年会(ワークショップ)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ビタミンDによるサルコペニアの予防・改善の分子基盤の解析2020

    • Author(s)
      亀井康富
    • Organizer
      ジャパンミルクコングレス2020オンライン(乳の学術連合:牛乳乳製品健康科学会議)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Gene regulation in skeletal muscle atrophy by a transcription factor FOXO12020

    • Author(s)
      Mamoru Oyabu, Kaho Takigawa, Yasutomi Kamei
    • Organizer
      The American Physiological Society’s (APS) Integrative Physiology of Exercise (IPE) 2020 conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comprehensive analysis on blood of skeletal muscle-specific PGC-1α overexpressing mice2020

    • Author(s)
      Takumi Sugimoto, Ran Uchitomi, Yukino Hatazawa, Shinji Miura, Yasutomi Kamei
    • Organizer
      The American Physiological Society’s (APS) Integrative Physiology of Exercise (IPE) 2020 conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of DNA methyltransferase 3a (Dnmt3a) in skeletal muscle of mice2020

    • Author(s)
      Mariko Fujita, Yukino Hatazawa, Mamoru Oyabu, Yuto Ohira, Kengo Ishihara, Kiyoshi Yoshioka, Yusuke Ono, Yasutomi Kamei
    • Organizer
      The American Physiological Society’s (APS) Integrative Physiology of Exercise (IPE) 2020 conference
    • Related Report
      2020 Annual Research Report
  • [Presentation] Atrophy associated transcription factor FOXO1 suppresses transcriptional coactivator PGC-1β gene expression in skeletal muscles2020

    • Author(s)
      Shiho Nakai, Mamoru Oyabu, Yukino Hatazawa, Shiori Akashi, Tadahiro Kitamura, Shinji Miura, Yasutomi Kamei
    • Organizer
      The American Physiological Society’s (APS) Integrative Physiology of Exercise (IPE) 2020 conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 運動・筋萎縮における骨格筋代謝制御2019

    • Author(s)
      亀井康富
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨格筋萎縮における遺伝子発現制御2019

    • Author(s)
      亀井康富
    • Organizer
      日本外科代謝栄養学会 第56回学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨格筋機能における遺伝子発現制御:筋萎縮と運動2019

    • Author(s)
      亀井康富
    • Organizer
      The 6th Diabetes Research Innovation Symposium
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Vitamin D attenuates FOXOl-target muscle atrophy gene expression2019

    • Author(s)
      Yasutomi Kamei, Takumi Onishi, Rintaro Matsuda, Ran Uchitomi, Yukino Hatazawa
    • Organizer
      Asian Congress of Nutrition 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 老齢マウス骨格筋の代謝変動2019

    • Author(s)
      亀井康富
    • Organizer
      日本基礎老化学会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 大豆イソフラボンはPGC-1βを活性化し筋細胞で脂肪酸酸化酵素遺伝子の発現を増加させる2019

    • Author(s)
      亀井康富、中井志帆、内富蘭、畑澤幸乃
    • Organizer
      日本肥満学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨格筋機能におけるビタミンDの役割2019

    • Author(s)
      亀井康富
    • Organizer
      第10回 栄養学を志す若手のためのフォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨格筋のアミノ酸代謝:運動による代謝活性化2019

    • Author(s)
      亀井康富
    • Organizer
      日本トリプトファン研究会 第 39 回学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] サルコペニア骨格筋の代謝変化2019

    • Author(s)
      亀井康富
    • Organizer
      機能性食品用ペプチド研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration2019

    • Author(s)
      Yasutomi Kamei
    • Organizer
      International Conference on Food Factors 2019 (ICoFF2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 栄養・代謝物シグナルと食品機能2022

    • Author(s)
      亀井 康富
    • Total Pages
      236
    • Publisher
      羊土社
    • ISBN
      9784758104029
    • Related Report
      2021 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

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

    • Related Report
      2021 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
      2020 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
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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