Mechanisms and predictions for fiber type switching of skeletal muscle

• Project/Area Number: 26282184
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Sports science
• Research Institution: University of Shizuoka
• Principal Investigator: Miura Shinji 静岡県立大学, 食品栄養科学部, 教授 (10342932)
• Co-Investigator(Kenkyū-buntansha): 守田 昭仁 静岡県立大学, 食品栄養科学部, 助教 (40239653)
• Co-Investigator(Renkei-kenkyūsha): KAMEI YASUTOMI 京都府立大学, 生命環境科学研究科, 教授 (70300829) ; KAWANO FUMINORI 松本大学, 健康科学研究科, 准教授 (90346156) ; FUKUSAKI EIICHIRO 大阪大学, 工学系研究科, 教授 (40273594) ; BIN SHUNTETSU 静岡県立大学, 薬学部, 助教 (10453060)
• Research Collaborator: SATO TOMOKI 静岡県立大学, 大学院 薬食生命科学総合学府 ; SENOO NANAMI 静岡県立大学, 大学院 薬食生命科学総合学府
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: リン脂質 / 筋線維タイプ変化 / 運動トレーニング / 筋萎縮 / PGC-1 / FOXO1 / メタボロミクス / lipidomics / 健康・スポーツ科学 / スポーツ生理学

Outline of Final Research Achievements

PGC-1α, identified as a nuclear receptor coactivator, promotes mitochondrial biogenesis. PGC-1α is induced in the skeletal muscle by exercise and controls many of the adaptations to physical activity. Overexpression of PGC-1α promoted fiber-type switch, mitochondrial biogenesis, increased exercise capacity, increased expression of fatty acid transporters, and enhanced angiogenesis and oxygen utilization kinetics in the skeletal muscle. In this study, we found that PGC-1α induced branched-chain amino acid metabolism and supplied substrates for the tricarboxylic acid cycle, which might also be involved in endurance capacity. We also found that exercise training increased phospholipids containing 22:6 fatty acids in glycolytic muscle and that PGC-1α was required for these alterations. Here, we present our findings on the PGC-1α isoforms, as well as recent findings on PGC-1α-induced changes in skeletal muscle phenotypes.

Research Products

• [Int'l Joint Research] University of Chicago(米国)
• [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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improved skeletal muscle Ca2+ regulation in vivo following contractions in mice overexpressing PGC-1α. (2017)
  • Author(s): Eshima, H., Miura, S., Senoo, N., Hatakeyama, K., Poole, D.C., and Kano, Y.
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 印刷中 Issue: 6 Pages: 1017-1028
  • DOI: 10.1152/ajpregu.00032.2017
  • Peer Reviewed / 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
  • Peer Reviewed / Int'l Joint Research / 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
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle. (2015)
  • Author(s): Senoo N, Miyoshi N, Goto-Inoue N, Minami K, Yoshimura R, Morita A, Sawada N, Matsuda J, Ogawa Y, Setou M, Kamei Y, Miura S.
  • Journal Title: J Lipid Res. Volume: 56 Issue: 12 Pages: 2286-96
  • DOI: 10.1194/jlr.m060533
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolomic Analysis of the Skeletal Muscle of Mice Overexpressing PGC-1α. (2015)
  • Author(s): Hatazawa Y, Senoo N, Tadaishi M, Ogawa Y, Ezaki O, Kamei Y, Miura S.
  • Journal Title: PLoS One. Volume: 10 Issue: 6 Pages: e0129084-e0129084
  • DOI: 10.1371/journal.pone.0129084
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glycerol 3-phosphate dehydrogenase 1 deficiency enhances exercise capacity due to increased lipid oxidation during strenuous exercise. (2015)
  • Author(s): Sato, T., Morita, A., Mori, N., and Miura, S.
  • Journal Title: Biochem Biophys Res Commun Volume: 457 Issue: 4 Pages: 653-658
  • DOI: 10.1016/j.bbrc.2015.01.043
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PGC-1α, a stimuli-inducible nuclear receptor coactivator: structural features and role in skeletal muscle metabolism gene regulation. (2015)
  • Author(s): Kamei, Y., Hatazawa, Y., Yoshimura, R., and Miura, S.
  • Journal Title: RNA and Transcription Volume: 1 Pages: 6-9
  • Peer Reviewed
• [Journal Article] The effects of PGC-1α on control of microvascular P(O2) kinetics following onset of muscle contractions. (2014)
  • Author(s): Kano Y, Miura S, Eshima H, Ezaki O, Poole DC.
  • Journal Title: J Appl Physiol Volume: 117 Issue: 2 Pages: 163-170
  • DOI: 10.1152/japplphysiol.00080.2014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle. (2014)
  • Author(s): Y. Hatazawa, M. Tadaishi, Y. Nagaike, A. Morita, Y. Ogawa, O. Ezaki, T. Takai-Igarashi, Y. Kitaura, Y. Shimomura, Y. Kamei*, S. Miura*
  • Journal Title: PLOS ONE Volume: 9 Issue: 3 Pages: e91006-e91006
  • DOI: 10.1371/journal.pone.0091006
  • Peer Reviewed / Open Access
• [Journal Article] The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice. (2014)
  • Author(s): Sato, T., Morita, A., Mori, N., and Miura, S.
  • Journal Title: Biochem Biophys Res Commun Volume: 444 Issue: 4 Pages: 525-530
  • DOI: 10.1016/j.bbrc.2014.01.096
  • Peer Reviewed
• [Journal Article] 運動と体の不思議を探るプロの知識・プロの技術「運動の分子生物学」 (2014)
  • Author(s): 三浦進司
  • Journal Title: 健康づくり Volume: 440 Pages: 12-15
• [Journal Article] Mechanisms of exercise- and training-induced fatty acid oxidation in skeletal muscle (2014)
  • Author(s): Miura, S., Tadaishi, M., Kamei, Y., and Ezaki, O.
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 3 Issue: 1 Pages: 43-53
  • DOI: 10.7600/jpfsm.3.43
  • NAID: 130003397904
  • ISSN: 2186-8123, 2186-8131
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle. (2017)
  • Author(s): Miura, S., Senoo, N., Miyoshi, N., Goto-Inoue, N., Minami, K., Yoshimura, R., Morita, A., Sawada, N., Matsuda, J., Ogawa, Y., Setou, M., and Kamei, Y.
  • Organizer: 12th China-Japan Symposium on Health Sciences
  • Place of Presentation: Hangzhou, China
  • Year and Date: 2017-02-10
  • Int'l Joint Research / Invited
• [Presentation] PGC-1αによる筋機能調節：運動を分子レベルから考える (2016)
  • Author(s): 三浦進司
  • Organizer: 第23回日本未病システム学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2016-11-05
  • Invited
• [Presentation] 筋萎縮時の骨格筋リン脂質分子種変化へのFOXO1の関与 (2016)
  • Author(s): 妹尾奈波、小林絵理、三好規之、守田昭仁、亀井康富、三浦進司
  • Organizer: 第７１回日本体力医学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2016-09-23
• [Presentation] PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle. (2016)
  • Author(s): Miura, S., Senoo, N., Miyoshi, N., Goto-Inoue, N., Minami, K., Yoshimura, R., Morita, A., Sawada, N., Matsuda, J., Ogawa, Y., Setou, M., and Kamei, Y.
  • Organizer: 57th International Conference on the Bioscience of Lipids
  • Place of Presentation: Chamonix Mont-Blanc, France
  • Year and Date: 2016-09-03
  • Int'l Joint Research
• [Presentation] FOXO1-induced atrophy changes in phospholipid profiles of skeletal muscle. (2016)
  • Author(s): Senoo, N., Miyoshi, N., Kobayashi, E., Morita, A., Kamei, Y., and Miura, S.
  • Organizer: 57th International Conference on the Bioscience of Lipids
  • Place of Presentation: Chamonix Mont-Blanc, France
  • Year and Date: 2016-09-03
  • Int'l Joint Research
• [Presentation] PGC-1α新規アイソフォーム発見と骨格筋への影響 (2016)
  • Author(s): 三浦進司
  • Organizer: 第24回日本運動生理学会大会
  • Place of Presentation: 熊本
  • Year and Date: 2016-07-23
  • Invited
• [Presentation] PGC-1αを介した運動トレーニングによる骨格筋リン脂質分子種の変化 (2016)
  • Author(s): 妹尾奈波、三好規之、井上菜穂子、守田昭仁、澤田直樹、松田潤一郎、小川佳宏、瀬藤光利、亀井康富、三浦進司
  • Organizer: 第58回日本脂質生化学会大会
  • Place of Presentation: 秋田
  • Year and Date: 2016-06-09
• [Presentation] FOXO1を介した筋萎縮時の骨格筋リン脂質分子種の変化 (2016)
  • Author(s): 三浦進司、妹尾奈波、三好規之、守田昭仁、亀井康富
  • Organizer: 第58回日本脂質生化学会大会
  • Place of Presentation: 秋田
  • Year and Date: 2016-06-09
• [Presentation] PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle. (2016)
  • Author(s): Miura, S., Senoo, N., Miyoshi, N., Goto-Inoue, N., Minami, K., Yoshimura, R., Morita, A., Sawada, N., Matsuda, J., Ogawa, Y., Setou, M., and Kamei, Y.
  • Organizer: Experimental Biology 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] FOXO1-induced atrophy changes in phospholipid profiles of skeletal muscle. (2016)
  • Author(s): Senoo, N., Miyoshi, N., Kobayashi, E., Morita, A., Kamei, Y., and Miura, S.
  • Organizer: Experimental Biology 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] 骨格筋PGC-1αによる代謝調節 (2016)
  • Author(s): 三浦進司、妹尾奈波、畑澤幸乃、只石幹、亀井康富、江崎治
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] 運動トレーニングによる骨格筋中リン脂質分子種の変化へのPGC-1αの関与 (2015)
  • Author(s): 妹尾奈波、三好規之、守田昭仁、亀井康富、三浦進司
  • Organizer: 第７０回日本体力医学会大会
  • Place of Presentation: 和歌山
  • Year and Date: 2015-09-19
• [Presentation] 骨格筋におけるエネルギー代謝制御研究の新展開 (2015)
  • Author(s): 三浦進司
  • Organizer: 第68回日本栄養・食糧学会中部支部大会
  • Place of Presentation: 静岡
  • Year and Date: 2015-07-18
  • Invited
• [Presentation] PGC-1 alpha mediated changes of phospholipids profile in exercise trained skeletal muscle (2015)
  • Author(s): Senoo, N., Miyoshi, N., Goto-Inoue, N., Morita, A., Sawada, N., Matsuda, J., Ogawa, Y., Setou, M., Kamei, Y., and Miura, S.
  • Organizer: Cell Symposia: Exercise Metabolism
  • Place of Presentation: Amsterdam
  • Year and Date: 2015-07-12
  • Int'l Joint Research
• [Presentation] Glycerol-3-phosphate dehydrogenase 1が運動持久力に及ぼす影響 (2014)
  • Author(s): 佐藤友紀、守田昭仁、森展子、三浦進司
  • Organizer: 第67回日本栄養・食糧学会中部支部大会
  • Place of Presentation: 静岡市
  • Year and Date: 2014-11-22
• [Presentation] The roles of GPD1 in exercise capacity. (2014)
  • Author(s): Sato T, Morita A, Mori N, Miura S
  • Organizer: The 19th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 沼津市
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] Establishment of in vitro screening system to identify functional foods activating PGC-1alpha and PPARs. (2014)
  • Author(s): Nagaike Y, Takeuchi A, Morita A, Kamei Y, Miura S
  • Organizer: The 19th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 沼津市
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] Exercise training changes lipid composition in the skeletal muscle -Lipidomics analysis of PGC-1 alpha overexpressing skeletal muscle-. (2014)
  • Author(s): Senoo N, Kobayashi E, Morita A, Kamei Y, Miyoshi N, Miura S
  • Organizer: The 19th Shizuoka Forum on Health and Longevity
  • Place of Presentation: 沼津市
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] 運動トレーニングによる骨格筋の遅筋特性獲得のメカニズム (2014)
  • Author(s): 三浦進司、妹尾奈波、三好規之、只石幹、亀井康富、江崎治
  • Organizer: 第６９回日本体力医学会大会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-09-19 – 2014-09-21
  • Invited
• [Presentation] 骨格筋代謝の遺伝子発現制御 (2014)
  • Author(s): 亀井康富、三浦進司
  • Organizer: 第６９回日本体力医学会大会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-09-19 – 2014-09-21
  • Invited
• [Presentation] 持久的トレーニングによる骨格筋での脂質組成変化 ～筋PGC-1αマウスでの検討～ (2014)
  • Author(s): 三浦進司、妹尾奈波、三好規之、守田昭仁、亀井康富
  • Organizer: 第６９回日本体力医学会大会
  • Place of Presentation: 長崎市
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] 転写共役因子を介する骨格筋アミノ酸代謝調節；遺伝子改変マウスを用いた解析 (2014)
  • Author(s): 畑澤幸乃、只石幹、長池祐太、守田昭仁、小川佳宏、江崎治、北浦靖之、下村吉治、亀井康富、三浦進司
  • Organizer: 第６８回日本栄養・食糧学会大会
  • Place of Presentation: 札幌市
  • Year and Date: 2014-05-30 – 2014-06-01
• [Presentation] 久的トレーニングによる骨格筋での脂質組成変化 ～筋PGC-1αマウスでの検討～ (2014)
  • Author(s): 妹尾奈波、三好規之、守田昭仁、亀井康富、三浦進司
  • Organizer: 第６８回日本栄養・食糧学会大会
  • Place of Presentation: 札幌市
  • Year and Date: 2014-05-30 – 2014-06-01
• [Presentation] PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle. (2014)
  • Author(s): Hatazawa, Y., Tadaishi, M., Nagaike, Y., Morita, A., Ogawa, Y., Ezaki, O., Kitaura, Y., Shimomura, Y., Kamei, Y., and Miura, S.
  • Organizer: Experimental Biology 2014
  • Place of Presentation: San Diego
  • Year and Date: 2014-04-26 – 2014-04-30
• [Remarks] 運動トレーニングによる骨格筋中リン脂質分子種の変化へのPGC-1αの関与
  • URL: http://dfns.u-shizuoka-ken.ac.jp/labs/nutrbioc/index3.html/Research9.html