Role of PGC1alpha and FOXO1 in skeletal muscle amino acid metabolism, and muscle mass

• Project/Area Number: 25292076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Kyoto Prefectural University
• Principal Investigator: Kamei Yasutomi 京都府立大学, 生命環境科学研究科(系), 教授 (70300829)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 骨格筋 / 転写調節 / 運動 / 代謝 / アミノ酸代謝 / BCAA / アミノ酸 / 遺伝子発現

Outline of Final Research Achievements

A well-balanced body energy budget is controlled by limiting calorie intake and/or increasing energy expenditure, which is typically achieved by appropriate physical exercise, and is the most effective treatment for obesity and diabetes mellitus. In this study, we showed that PGC1α and FOXO1 are critical regulators of amino acid metabolism in skeletal muscle (BCAA and glutamine, respectively). Our aims are to better understand the molecular mechanisms underlying skeletal muscle metabolism, establish novel strategies for the prevention of lifestyle-related diseases and sarcopenia, and establish a fundamental biological basis for the effects of functional foods.

Research Products

• [Journal Article] FOXO1 delays skeletal muscle regeneration and suppresses myoblast proliferation. (2016)
  • Author(s): Yamashita A, Hatazawa Y, Hirose Y, Ono Y, Kamei Y
  • Journal Title: Biosci Biotechnol Biochem Volume: 未定
  • Peer Reviewed / 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] Down Regulation of Asparagine Synthetase and 3-Phosphoglycerate Dehydrogenase, and the Up-Regulation of Serine Dehydratase in Rat Liver from Intake of Excess Amount of Leucine Are Not Related to Leucine-Caused Amino Acid Imbalance (2015)
  • Author(s): Yoshimura, R., Takai, M., Namaki, H., Minami, K., Imamura, W., Kato, H., Kamei, Y., and Kanamoto, R.
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 61 Issue: 6 Pages: 441-448
  • DOI: 10.3177/jnsv.61.441
  • NAID: 130005125480
  • ISSN: 0301-4800, 1881-7742
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity. (2015)
  • Author(s): Morita S, Nakabayashi K, Kawai T, Hayashi K, Horii T, Kimura M, Kamei Y, Ogawa Y, Hata K, Hatada I
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 21693-21693
  • DOI: 10.1038/srep21693
  • Peer Reviewed / Open Access
• [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] ATM regulates adipocyte differentiation and contributes to glucose homeostasis. (2015)
  • Author(s): Takagi M., Uno M., Nishii R., Sugimoto M., Hasegawa S., Piao J., Ihara N., Kanai S., Kakei S., Tamura Y., Suganami T., Kamei Y., Shimizu T., Yasuda A., Ogawa Y., Mizutani S.
  • Journal Title: Cell Reports Volume: 10 Issue: 6 Pages: 957-967
  • DOI: 10.1016/j.celrep.2015.01.027
  • Peer Reviewed / Open Access
• [Journal Article] Ligand-activated PPARα-dependent DNA demethylation regulates the fatty acid β-oxidation genes in the postnatal liver. (2014)
  • Author(s): Ehara T, Kamei Y, Yuan X, Takahashi M, Kanai S, Tamura E, Tsujimoto K, Tamiya T, Nakagawa Y, Shimano H, Takai-Igarashi T, Hatada I, Suganami T, Hashimoto K, Ogawa Y.
  • Journal Title: Diabetes. Volume: 64(3) Issue: 3 Pages: 775-84
  • DOI: 10.2337/db14-0158
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] FOXO1 activates glutamine synthetase gene in mouse skeletal muscles through a region downstream of 3'-UTR: possible contribution to ammonia detoxification. (2014)
  • Author(s): Kamei Y, Hattori M, Hatazawa Y, Kasahara T, Kanou M, Kanai S, Yuan X, Suganami T, Lamers WH, Kitamura T, Ogawa Y.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 307
  • 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] Endothelial PGC-1α mediates vascular dysfunction in diabetes (2014)
  • Author(s): N. Sawada, A. Jiang, F. Takizawa, A. Safdar, A. Manika, Y. Tesmenitsky, K.-T. Kang, J. Bischoff, H. Kalwa, J.L. Sartoretto, Y. Kamei, L.E. Benjamin, H. Watada, Y. Ogawa, Y. Higashikuni, C.W. Kessinger, F.A. Jaffer, T. Michel, M. Sata, K. Croce, R. Tanaka, Z Arany
  • Journal Title: Cell Metab Volume: 19 Issue: 2 Pages: 246-58
  • DOI: 10.1016/j.cmet.2013.12.014
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of Pgc-1α expression by tea leaves and their by-products (2014)
  • Author(s): Shibuya E, Murakami M, Kondo M, Kamei Y, Tomonaga S, Matsui T, Funaba M
  • Journal Title: Cell Biochem Funct Volume: 32 Issue: 3 Pages: 236-40
  • DOI: 10.1002/cbf.3006
  • NAID: 120005623240
  • Peer Reviewed
• [Journal Article] Mechanisms of exercise- and training-induced fatty acid oxidation in skeletal muscle. (2014)
  • Author(s): S. Miura, M. Tadaishi, Y. Kamei, O. Ezaki.
  • Journal Title: J. Physical Fitness and Sports Medicine Volume: 印刷中
  • NAID: 130003397904
  • Peer Reviewed
• [Journal Article] FoxO1 Inhibits Skeletal Muscle Hypertrophy Through mTOR-independent Mechanisms. (2013)
  • Author(s): R. A. Potter, A. D. DeLong, S. M. Smith, B. M. Erb, B. Renwand, Y. Kamei, Y. Ogawa, T. J. McLoughlin.
  • Journal Title: Journal of Exercise Physiology Volume: 16 Pages: 32-50
  • Peer Reviewed
• [Presentation] 骨格筋の代謝におけるアミノ酸の機能と分子機序 (2015)
  • Author(s): 亀井康富
  • Organizer: 国際アミノ酸学会
  • Place of Presentation: 東京
  • Year and Date: 2015-12-11
  • Invited
• [Presentation] 運動や栄養環境変化による遺伝子発現変化と生活習慣病予防 (2015)
  • Author(s): 亀井康富
  • Organizer: 第６回岐阜薬科大学機能性健康食品（蜂産品）研究講演会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] 骨格筋PGC1α欠損マウスへのBCAA摂取による脳内キヌレン酸量の減少 (2015)
  • Author(s): 亀井康富、関根愛莉、吉村亮二、南貴美子、福渡努
  • Organizer: アミノ酸学会
  • Place of Presentation: 滋賀
  • Year and Date: 2015-10-23
• [Presentation] 生活習慣病に関する遺伝子発現制御 (2015)
  • Author(s): 亀井康富
  • Organizer: 第４回 奥伊勢Forum
  • Place of Presentation: 三重
  • Year and Date: 2015-10-16
  • Invited
• [Presentation] Skeletal muscle metabolism during exercise and its interaction with obesity (2015)
  • Author(s): 亀井康富
  • Organizer: Kyoto Conference of Young Lions in Obesity Research
  • Place of Presentation: 京都
  • Year and Date: 2015-10-05
  • Int'l Joint Research / Invited
• [Presentation] マウス骨格筋において転写共役因子PGC1αはBCAA代謝を促進する (2015)
  • Author(s): 亀井康富、畑澤幸乃、只石幹、小川佳宏、北浦靖之、下村吉治、三浦進司
  • Organizer: 日本肥満学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-02
• [Presentation] 骨格筋のエネルギー代謝制御因子PGC1α (2015)
  • Author(s): 亀井康富、三浦進司
  • Organizer: 日本農芸化学会中部・関西支部合同大会
  • Place of Presentation: 富山
  • Year and Date: 2015-09-19
• [Presentation] PGC1α-Tgマウスの骨格筋におけるメタボローム解析 (2015)
  • Author(s): 亀井康富、畑澤幸乃、妹尾奈波、小川佳宏、三浦進司
  • Organizer: 日本肥満学会adiposcienceシンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2015-08-22
• [Presentation] 骨格筋代謝と肥満―マウスモデルを用いた検討― (2015)
  • Author(s): 亀井康富
  • Organizer: 第２３回日本運動生理学会大会シンポジウム
  • Place of Presentation: 東京都品川区
  • Year and Date: 2015-07-26
  • Invited
• [Presentation] Molecular mechanism of gene expression in skeletal muscle function and amino acid metabolism (2015)
  • Author(s): Yasutomi Kamei, Shinji Miura, Yoshihiro Ogawa
  • Organizer: 12TH Asian Congress of Nutrition
  • Place of Presentation: 横浜
  • Year and Date: 2015-05-14
  • Int'l Joint Research / Invited
• [Presentation] 核内受容体・転写共役因子と骨格筋代謝 (2014)
  • Author(s): 亀井康富
  • Organizer: 第一回バイオ・フロンティア・プラットフォームシンポジウム
  • Place of Presentation: 京都府京都市
  • Year and Date: 2014-12-01
  • Invited
• [Presentation] FOXO1は骨格筋のグルタミン代謝を活性化する (2014)
  • Author(s): 亀井康富、服部真季、畑澤幸乃、金井紗綾香、北村忠弘、小川佳宏
  • Organizer: 日本アミノ酸学会 第8回学術大会
  • Place of Presentation: 東京都世田谷区
  • Year and Date: 2014-11-08
  • 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: 長崎県長崎市
  • Year and Date: 2014-09-19
  • Invited
• [Presentation] FOXO1 activates glutamine synthetase gene in mouse skeletal muscles (2014)
  • Author(s): Yasutomi Kamei, Maki Hattori, Yukino Hatazawa, Tomomi Kasahara, Tadahiro Kitamura, Yoshihiro Ogawa
  • Organizer: Experimental Biology 2014
  • Place of Presentation: 米国カリフォルニア州
  • Year and Date: 2014-04-28
• [Presentation] 骨格筋アミノ酸代謝における遺伝子発現制御 (2014)
  • Author(s): 亀井 康富
  • Organizer: 2014年度日本農芸化学会大会（シンポジウム）
  • Place of Presentation: 神奈川県川崎市
  • Year and Date: 2014-04-01
  • Invited
• [Presentation] 核内受容体コファクターによる骨格筋アミノ酸代謝制御 (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: 日本農芸化学会大会
  • Place of Presentation: 神奈川
• [Presentation] 遺伝子改変動物を用いた筋サテライト細胞の分化能解析 (2014)
  • Author(s): 山下敦史、畑澤幸乃、吉村亮二、小川祥加、小野悠介、亀井康富
  • Organizer: 日本農芸化学会関西支部第 483 回 講演会
  • Place of Presentation: 京都
• [Presentation] ロイシン摂取によるmTORC1経路活性化に及ぼすPGC-1αの影響 (2013)
  • Author(s): 吉村亮二、佐藤沙耶、南貴美子、只石幹、三浦進司、亀井康富
  • Organizer: 日本農芸化学会関西支部第 482 回 講演会
  • Place of Presentation: 神戸
• [Presentation] マウス骨格筋における転写共役因子PGC-1αによるBCAA代謝調節 (2013)
  • 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52回 日本栄養・食糧学会 近畿支部大会
  • Place of Presentation: 滋賀
• [Presentation] 骨格筋機能と遺伝子発現制御 (2013)
  • Author(s): 亀井康富
  • Organizer: 日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
  • Invited
• [Book] 月刊糖尿病 骨格筋からみた糖尿病の病態と治療 (2015)
  • Author(s): 亀井康富，小川佳宏
  • Publisher: 医学出版
• [Book] 化学と生物 骨格筋と脂肪組織にかかわる最近の話題 (2015)
  • Author(s): 山下敦史、亀井康富
  • Publisher: 日本農芸化学会
• [Book] 骨格筋とオートファジー (2015)
  • Author(s): 吉村亮二、亀井康富
  • Publisher: 内分泌・糖尿病・代謝内科
• [Book] 化学と生物「骨格筋と脂肪組織にかかわる最近の話題」 (2015)
  • Author(s): 山下敦史、亀井康富
  • Total Pages: 1
  • Publisher: 日本農芸化学会 会誌
• [Book] 月刊糖尿病 「骨格筋からみた糖尿病の病態と治療」 (2014)
  • Author(s): 亀井康富，小川佳宏
  • Total Pages: 6
  • Publisher: 医学出版
• [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/
• [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/