Regulating mechanism of mitochondrial function by BDNF in the skeletal muscle

• Project/Area Number: 26750331
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Hokkaido University
• Principal Investigator: Takada Shingo 北海道大学, 医学研究科, 博士研究員 (60722329)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ミトコンドリア / 骨格筋 / マイオカイン / 心不全 / 老化・加齢 / マイトファジー / 脳由来神経栄養因子 / ミトコンドリアダイナミクス / 運動能力 / ミトコンドリア機能 / 老化 / エネルギー代謝 / 筋収縮

Outline of Final Research Achievements

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, has been known to be increased by exercise training and associated with exercise capacity (Int J Cardiol 2013), which are dependent on mitochondrial function in the skeletal muscle. BDNF-TrkB pathway may play an important role in the improvement of the beneficial effects of exercise training on the exercise capacity and skeletal muscle mitochondrial function.

Research Products

• [Journal Article] Inverse Relationship between Sleep Duration and Cardio-Ankle Vascular Index in Children (2017)
  • Author(s): Morita N, Kambayashi I, Okuda T, Oda S, Takada S, Nakajima T, Shide N, Shinkaiya H, Okita K.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 24 Issue: 8 Pages: 819-826
  • DOI: 10.5551/jat.36517
  • NAID: 130005876106
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome (2017)
  • Author(s): Yokota T, Kinugawa S, Hirabayashi K, Suga T, Takada S, Omokawa M, Kadoguchi T, Takahashi M, Fukushima A, Matsushima S, Yamato M, Okita K, Tsutsui H
  • Journal Title: J Diabetes Investig Volume: 印刷中 Issue: 4 Pages: 1-6
  • DOI: 10.1111/jdi.12606
  • NAID: 120006337767
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes. (2016)
  • Author(s): Mizushima, W., Takahashi , H., Watanabe, M., Kinugawa, S., Matsushima, S., Takada, S., Yokota, T., Furihata, T., Matsumoto, J., Tsuda, M., Chiba, I., Nagashima, S., Yanagi, S., Matsumoto, M., Nakayama, K.I., Tsutsui, H. and Hatakeyama, S.
  • Journal Title: J. Mol. Cell. Cardiol. Volume: 100 Pages: 43-53
  • DOI: 10.1016/j.yjmcc.2016.09.013
  • NAID: 120006360069
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dipeptidyl peptidase-4 inhibitor improved exercise capacity and mitochondrial biogenesis in mice with heart failure via activation of GLP-1 receptor signaling. (2016)
  • Author(s): Takada S, Masaki Y, Kinugawa S, Matsumoto J, Furihata T, Mizushima W, Kadoguchi T, Fukushima A, Homma T, Takahashi M, Harashima S, Matsushima S, Yokota T, Tanaka S, Okita K, Tsutsui H
  • Journal Title: Cardiovasc Res Volume: 111 Issue: 4 Pages: 338-347
  • DOI: 10.1093/cvr/cvw182
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The experimental model of transition from compensated cardiac hypertrophy to failure created by transverse aortic constriction in mice. (2016)
  • Author(s): Furihata T, Kinugawa S, Takada S, Fukushima A, Takahashi M, Homma T, Masaki Y, Tsuda M, Matsumoto J, Mizushima W, Matsushima S, Yokota T, Tsutsui H.
  • Journal Title: IJC Heart & Vasculature Volume: 11 Pages: 24-28
  • DOI: 10.1016/j.ijcha.2016.03.007
  • NAID: 120005855964
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Serum Myostatin Levels are Independently Associated with Skeletal Muscle Wasting in Patients with Heart Failure. (2016)
  • Author(s): Furihata T, Kinugawa S, Fukushima A, Takada S, Homma T, Masaki Y, Abe T, Yokota T, Oba K, Okita K, Tsutsui H.
  • Journal Title: International Journal of Cardiology Volume: 220 Pages: 483-487
  • DOI: 10.1016/j.ijcard.2016.06.231
  • NAID: 120006347185
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Direct renin inhibitor ameliorated insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice. (2016)
  • Author(s): Fukushima A, Kinugawa S, Takada S, Matsumoto J, Furihata T, Mizushima W, Tsuda M, Yokota T, Matsushima S, Okita K, Tsutsui H
  • Journal Title: Eur J Pharmacol Volume: 779 Pages: 147-156
  • DOI: 10.1016/j.ejphar.2016.03.022
  • NAID: 120006219992
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] フレイル！ 心リハの視点から「知りたい！フレイル患者さんの運動療法」 (2016)
  • Author(s): 沖田孝一，髙田真吾，阿部隆宏，米澤一也．
  • Journal Title: ハートナーシング Volume: 29 Pages: 99-103
• [Journal Article] 心疾患における運動の意義． (2016)
  • Author(s): 髙田真吾，沖田孝一．
  • Journal Title: 日本未病システム学会雑誌 Volume: 22 Pages: 1-4
• [Journal Article] CKD患者のサルコペニア・フレイル．筋肉代謝の基礎 (2016)
  • Author(s): 沖田孝一，髙田真吾．
  • Journal Title: 腎と透析 Volume: 80 Pages: 636-640
• [Journal Article] Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high-fat diet-induced diabetes (2015)
  • Author(s): Takada S, Kinugawa S, Matsushima S, Takemoto D, Furihata T, Mizushima W, Fukushima A, Yokota T, Ono Y, Shibata H, Okita K, Tsutsui H
  • Journal Title: Exp Physiol Volume: 100 Issue: 11 Pages: 1319-30
  • DOI: 10.1113/ep085251
  • Peer Reviewed / Open Access
• [Journal Article] Small conductance Ca2+-activated K+ current is upregulated via the phosphorylation of CaMKII in cardiac hypertrophy from spontaneously hypertensive rats. (2015)
  • Author(s): Mizukami K, Yokoshiki H, Mitsuyama H, Watanabe M, Tenma T, Takada S, Tsutsui H.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 309 Issue: 6 Pages: H1066-H1074
  • DOI: 10.1152/ajpheart.00825.2014
  • Peer Reviewed
• [Journal Article] Low-intensity exercise under ischemic conditions enhances metabolic stress in patients with heart failure (2015)
  • Author(s): Takahashi M, Kinugawa S, Takada S, Hirabayashi K, Yokota T, Matsushima S, Saito A, Okita K, Tsutsui H
  • Journal Title: Int J Cardiol Volume: 201 Pages: 142-4
  • DOI: 10.1016/j.ijcard.2015.08.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Curcumin ameliorates skeletal muscle atrophy in type I diabetic mice via inhibiting the protein ubiqutination (2015)
  • Author(s): Ono T, Takada S, Kinugawa S, Tsutsui H
  • Journal Title: Exp Physiol Volume: 100 Issue: 9 Pages: 1052-1063
  • DOI: 10.1113/ep085049
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress. (2015)
  • Author(s): Nishikawa M, Ishimori N, Takada S, Saito A, Kadoguchi T, Furihata T, Fukushima A, Matsushima S, Yokota T, Kinugawa S, Tsutsui H
  • Journal Title: Nephrol Dial Transplant. Volume: in press Issue: 6 Pages: 182-188
  • DOI: 10.1093/ndt/gfv103
  • NAID: 120005743055
  • Peer Reviewed
• [Journal Article] Serum brain-derived neurotrophic factor level predicts adverse clinical outcomes in patients with heart failure (2015)
  • Author(s): Fukushima A, Kinugawa S, Homma T, Masaki Y, Furihata T, Yokota T, Matsushima S, Takada S, Kadoguchi T, Oba K, Okita K, Tsutsui H
  • Journal Title: J Card Fail Volume: 21 Issue: 4 Pages: 300-306
  • DOI: 10.1016/j.cardfail.2015.01.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative fibre number and induce atrophy in mouse hindlimb skeletal muscle. (2015)
  • Author(s): Kadoguchi T, Kinugawa S, Takada S, Fukushima A, Furihata T, Homma T, Masaki Y, Mizushima W, Nishikawa M, Takahashi M, Yokota T, Matsushima S, Okita K, Tsutsui H
  • Journal Title: Exp Physiol Volume: 100 Issue: 3 Pages: 312-322
  • DOI: 10.1113/expphysiol.2014.084095
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Skeletal Muscle Abnormalities in Heart Failure (2015)
  • Author(s): Kinugawa S, Takada S, Matsushima S, Okita K, Tsutsui H
  • Journal Title: International Heart Journal Volume: 56 Issue: 5 Pages: 475-484
  • DOI: 10.1536/ihj.15-108
  • NAID: 130005102118
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] (Pro)renin receptor in skeletal muscle is involved in the development of insulin resistance associated with postinfarct heart failure in mice (2014)
  • Author(s): Fukushima A, Kinugawa S, Takada S, Matsushima S, Sobirin MA, Ono T, Takahashi M, Suga T, Homma T, Masaki Y, Furihata T, Kadoguchi T, Yokota T, Okita K, Tsutsi H
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 307
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intramyocellular Lipid is Increased in the Skeletal Muscle of Patients with Dilated Cardiomyopathy with Lowered Exercise Capacity (2014)
  • Author(s): Hirabayashi K, Kinugawa S, Yokota T, Takada S, Fukushima S, Suga T, Takahashi M, Ono T, Morita N, Omokawa M, Harada K, Oyama-Manabe N, Shirato H, Matsushima S, Okita K, Tsutsui H
  • Journal Title: Int J Cardiol Volume: 176 Pages: 1110-1112
  • NAID: 120006809251
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice (2014)
  • Author(s): Suga T, Kinugawa S, Takada S, Kadoguchi T, Fukushima A, Homma T, Masaki Y, Furihata T, Takahashi M, Sobirin MA, Ono T, Hirabayashi K, Yokota T, Tanaka S, Okita K, Tsutsui H
  • Journal Title: Endocrinology Volume: 155 Pages: 68-80
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice (2014)
  • Author(s): Takada S, Hirabayashi K, Kinugawa S, Yokota T, Matsushima S, Suga T, Kadoguchi T, Fukushima A, Homma T, Mizushima W, Masaki Y, Furihata T, Katsuyama R, Okita K, Tsutsui H
  • Journal Title: Eur J Pharmacol Volume: 740 Pages: 690-696
  • NAID: 120005476207
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] The novel heart-specific RING-finger protein 207 modulates energy metabolism in cardiomyocytes. (2017)
  • Author(s): Takada S, Mizushima W, Furihata T, Matsumoto J, Tsuda M, Katayama T, Nakajima T, Yokota T, Kinugawa S.
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2017-03-16
• [Presentation] 骨格筋・心筋ミトコンドリア治療 (2017)
  • Author(s): 髙田真吾
  • Organizer: 日本女子大学講演
  • Place of Presentation: 日本女子大学
  • Year and Date: 2017-02-17
  • Invited
• [Presentation] Exercise is medicine（介護における運動療法） (2016)
  • Author(s): 髙田真吾
  • Organizer: 相馬の里 特別出張講義
  • Place of Presentation: 株式会社相馬の里
  • Year and Date: 2016-11-27
  • Invited
• [Presentation] 運動による健康寿命の延伸 ～若返り、脳機能改善～ (2016)
  • Author(s): 髙田真吾
  • Organizer: 平成２８年度北翔大学・北海道大学・未来講義．
  • Place of Presentation: 原町生涯学習センター「サンライフ南相馬」
  • Year and Date: 2016-11-26
  • Invited
• [Presentation] 血流制限下レジスタンストレーニングの有用性：近赤外線分光法による組織酸素動態 (2016)
  • Author(s): 髙田真吾
  • Organizer: 第23回医用近赤外線分光法研究会
  • Place of Presentation: 持田製薬株式会社 本社 ルークホール
  • Year and Date: 2016-10-29
  • Invited
• [Presentation] mitoNEET蛋白はミトコンドリアの鉄恒常性を調節する． (2016)
  • Author(s): 髙田真吾，降旗高明，横田卓，沖田孝一，絹川真太郎．
  • Organizer: 第71回日本体力医学会学術集会
  • Place of Presentation: いわて県民情報交流センター（アイーナ）、盛岡地域交流センター市民文化ホール（マリオス）
  • Year and Date: 2016-09-23
• [Presentation] mitoNEETにおける心筋ミトコンドリア鉄制御 (2016)
  • Author(s): 髙田真吾
  • Organizer: 第4回北海道若手交流会
  • Place of Presentation: sapporo55
  • Year and Date: 2016-08-29
• [Presentation] ミトコンドリア鉄におけるmitoNEETの役割 (2016)
  • Author(s): 髙田真吾
  • Organizer: 1st Hokkaido Exercise and Cardiovascular Health Research meeting
  • Place of Presentation: 札幌医科大学(札幌市)
  • Year and Date: 2016-08-11
• [Presentation] 心筋梗塞後心不全における骨格筋ミトコンドリア機能および運動能力に対するGLP-1受容体の役割解明 (2016)
  • Author(s): 髙田真吾，正木芳宏，松本純一，門口智泰，横田 卓，水島 航，降旗高明，津田正哉，中島孝之，片山貴史，福島 新，沖田孝一，絹川真太郎．
  • Organizer: 第二回日本筋学会学術集会
  • Place of Presentation: 国立精神・神経医療研究センター
  • Year and Date: 2016-08-05
• [Presentation] 老化ミトコンドリアにおける脳由来神経栄養因子（BDNF）の役割 (2016)
  • Author(s): 髙田真吾
  • Organizer: 第7回Young Diabetologia & Cardiologist Forum
  • Place of Presentation: TKPガーデンシティ札幌駅前
  • Year and Date: 2016-07-28
  • Invited
• [Presentation] 脳由来神経栄養因子（BDNF）は加齢による骨格筋ミトコンドリア機能および運動能力低下を改善する (2016)
  • Author(s): 髙田真吾，絹川真太郎，横田 卓，水島 航，降旗高明，松本純一，津田正哉，中島孝之，片山貴史，沖田孝一，筒井裕之．
  • Organizer: 第22回日本心臓リハビリテーション学会学術集会（YIAセッション）
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-07-16
• [Presentation] 骨格筋の肥大と萎縮の分子生物学的機序． (2016)
  • Author(s): 絹川真太郎，髙田真吾，沖田孝一．
  • Organizer: 第51回日本理学療法学術集会
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2016-05-27
• [Presentation] 分子生物学的観点から糖尿病患者の筋機能の可能性を探る 糖尿病における筋機能異常． (2016)
  • Author(s): 沖田孝一，髙田真吾，横田 卓，絹川真太郎．
  • Organizer: 第51回日本理学療法学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2016-05-27
• [Presentation] トピックス：サルコペニア、フレイル、マイオカインとは？ (2015)
  • Author(s): 髙田真吾，絹川真太郎，沖田孝一，筒井裕之
  • Organizer: 第31回日本冠疾患学会
  • Place of Presentation: ロイトン札幌、北海道、札幌市
  • Year and Date: 2015-11-20
  • Invited
• [Presentation] Recombinant Human BDNF Can Mimic Effects of Exercise Training in Mice. (2015)
  • Author(s): Takada S, Kinugawa S, Matsushima S, Yokota T, Mizushima W, Furihata T, Matsumoto J, Tsuda M, Fukushima A, Okita K, Tsutsui H.
  • Organizer: 88th Scientific Session of American Heart Association
  • Place of Presentation: Orange County Convention Ctr, Orlando, Florida, USA.
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] 心不全モデルマウスにおける骨格筋ミトコンドリア機能低下に対する脳由来神経栄養因子の役割解明． (2015)
  • Author(s): 髙田真吾，絹川真太郎，横田 卓，松島将士，沖田孝一，筒井裕之．
  • Organizer: 第70回日本体力医学会
  • Place of Presentation: 和歌山県民文化会館、和歌山県、和歌山市
  • Year and Date: 2015-09-18
• [Presentation] 第10回Vascular Biology Innovation Conference (2015)
  • Author(s): 髙田真吾，絹川真太郎，横田 卓，松島将士，沖田孝一，筒井裕之
  • Organizer: 骨格筋における BDNF-TrkB シグナルの役割解明
  • Place of Presentation: ホテル椿山荘東京、東京都、文京区
  • Year and Date: 2015-08-22
  • Invited
• [Presentation] DPP-4 inhibitor improved exercise capacity in mice with heart failure. (2015)
  • Author(s): Takada S, Kinugawa S, Masaki Y, Kadoguchi T, Fukushima A, Furihata T, Kudo M, Matsumoto J, Tsuda M, Matsushima S, Yokota T, Okita K, Tsutsui H.
  • Organizer: 第21回日本心臓リハビリテーション学会学術集会
  • Place of Presentation: 福岡国際会議場、福岡県、福岡市
  • Year and Date: 2015-07-18
• [Presentation] DPP4阻害薬の他臓器への多面的効果－基礎から臨床へ (2015)
  • Author(s): 髙田真吾
  • Organizer: クリニカルサイエンス談話会2015
  • Place of Presentation: ホテルオークラ札幌、北海道、札幌市
  • Year and Date: 2015-04-24
  • Invited
• [Presentation] Brain-Derived Neurotrophic Factor Maintains Exercise Capacity And Mitochondrial Function In The Skeletal Muscle Through Ampk-Pgc1α Signaling (2014)
  • Author(s): Takada S, Kinugawa S, Matsushima S, Mizushima W, Fukushima A, Furihata T, Kadoguchi T, Yokota T, Suga T, Okita K, Tsutsui H
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 心筋梗塞後心不全における骨格筋ミトコンドリア機能および運動能力に対するDPP-4阻害薬の効果 (2014)
  • Author(s): 髙田真吾，絹川真太郎，正木芳宏，菅 唯志，門口智泰，沖田孝一，筒井裕之
  • Organizer: 第69回日本体力医学会
  • Place of Presentation: 長崎大学文京キャンパス（長崎県、長崎市）
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] Sesamin Improves Lowered Exercise Capacity, Mitochondrial Dysfunction in the Skeletal Muscle from High Fat Diet-Induced Diabetic Mice (2014)
  • Author(s): Takada S, Kinugawa S, Takemoto D, Masaki Y, Kadoguchi T, Yokota T, Matsushima S, Fukushima A, Homma T,Furihata T, Suga T, Katsuyama R, Ono Y, Shibata H, Okita K, Tsutsui H
  • Organizer: 50th EASD Annual Meeting 2014
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2014-09-15 – 2014-09-18
• [Presentation] BDNFは骨格筋ミトコンドリア機能および運動能力を制御する (2014)
  • Author(s): 髙田真吾、絹川真太郎、門口智泰、沖田孝一、筒井裕之
  • Organizer: 第20回日本心臓リハビリテーション学会
  • Place of Presentation: 京都市勧業館みやこめっせ（京都、京都市）
  • Year and Date: 2014-07-19 – 2014-07-20