Insulin signaling as a therapeutic target of heart failure

• Project/Area Number: 24591094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: SHIOI Tetsuo 京都大学, 医学(系)研究科(研究院), 講師 (50360095)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 心不全 / インスリン / ミトコンドリア / 悪液質

Outline of Final Research Achievements

Heart failure (HF) is associated with changes in energy metabolism of the heart, as well as in extra-cardiac organs such as skeletal muscles. We tested the hypothesis that BCAA ameliorate HF. We used Dahl salt-sensitive (DS) rats fed a high-salt diet as a model of HF. In HF rats, BCAA treatment decreased the heart rate, preserved the cardiac function, and prolonged survival. BCAA also prevented body weight loss, associated with preservation of the skeletal muscle weight. Moreover, the decrease of gene expression related to mitochondrial biogenesis and function was prevented by BCAA in skeletal muscles. In conclusion, BCAA ameliorated HF in a rat model.

Research Products

• [Journal Article] Relationships between nutritional status and markers of congestion in patients with pulmonary arterial hypertension (2015)
  • Author(s): Kawamoto A, Kato T, Minamino-Muta E, Okano Y, Shioi T, Kimura T
  • Journal Title: Int J Cardiol. Volume: 187 Pages: 27-28
  • NAID: 120006305980
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure (2015)
  • Author(s): Kawamoto A, Kato T, Shioi T, Okuda J, Kawashima T. Tamaki Y, Niizuma S, Tanada Y, Takemura G, Narazaki M, Matsuda T, Kimura T
  • Journal Title: PLoS One. Volume: 10 Issue: 1 Pages: e0117091-e0117091
  • DOI: 10.1371/journal.pone.0117091
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhanced cardiac Akt/protein kinase B signaling contributes to pathological cardiac hypertrophy in part by impairing mitochondrial function via transcriptional repression of mitochondrion-targeted nuclear genes (2014)
  • Author(s): Wende AR, O'Neill BT, Bugger H, Riehle C, Tuinei J, Buchanan J, Tsushima K, Wang L, Caro P, Guo A, Sloan C, Kim BJ, Wang X, Pereira RO, McCrory MA, Nye BG, Benavides GA, Darley-Usmar VM, Shioi T, Weimer BC, Abel ED
  • Journal Title: Mol Cell Biol. Volume: 35 Issue: 5 Pages: 831-846
  • DOI: 10.1128/mcb.01109-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Persistent overexpression of phosphoglycerate mutase, a glycolytic enzyme, modifies energy metabolism and reduces stress resistance of heart in mice (2013)
  • Author(s): Okuda, J., Niizuma, S., Shioi, T., Kato, T., Inuzuka, Y., Kawashima, T., Tamaki, Y., Kawamoto, A., Tanada, Y., Iwanaga, Y., Narazaki, M., Matsuda, T., Adachi, S., Soga, T., Takemura, G., Kondoh, H., Kita, T., Kimura, T.
  • Journal Title: PLoS ONE Volume: 8 Issue: 8 Pages: e72173-e72173
  • DOI: 10.1371/journal.pone.0072173
  • Peer Reviewed
• [Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts (2013)
  • Author(s): Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 72-81
  • DOI: 10.1016/j.yjmcc.2013.01.007
  • Peer Reviewed
• [Journal Article] Analysis of liver metabolism in a rat model of heart failure. (2012)
  • Author(s): Kato T, Niizuma S, Inuzuka Y, Kawashima T, Okuda J, Kawamoto A, Tamaki Y, Iwanaga Y, Soga T, Kita T, Kimura T, Shioi T.
  • Journal Title: Int J Cardiol. Volume: 161 Pages: 130-136
  • Peer Reviewed
• [Journal Article] Effect of persistent activation of phosphoinositide 3-kinase on heart. (2012)
  • Author(s): Niizuma S, Inuzuka Y, Okuda J, Kato T, Kawashima T, Tamaki Y, Iwanaga Y, Yoshida Y, Kosugi R, Watanabe-Maeda K, Machida Y, Tsuji S, Aburatani H, Izumi T, Kita T, Kimura T, Shioi T.
  • Journal Title: Life Sci. Volume: 90 Pages: 619-628
• [Presentation] A metabolic profile of fasted mice (2015)
  • Author(s): 牟田恵理, 棚田洋平, 加藤貴雄, 木村剛, 塩井哲雄
  • Organizer: 新学術領域「統合的多階層生体機能学領域の確立とその応用」最終成果報告会
  • Place of Presentation: 大阪
  • Year and Date: 2015-03-04 – 2015-03-05
• [Presentation] 心臓エネルギー代謝の頑健性とその破綻のメカニズムの統合的解明 (2014)
  • Author(s): 塩井哲雄
  • Organizer: 新学術領域「統合的多階層生体機能学領域の確立とその応用」第9回（平成26年度第1回）領域全体会議・研究報告会
  • Place of Presentation: 秋田
  • Year and Date: 2014-08-04 – 2014-08-06
• [Presentation] Branched-chain amino acids prevent heart failure in rats (2014)
  • Author(s): Tanada Y, Shioi T, Kawamoto A, Okuda J, Kimura T
  • Organizer: International academy of cardiology, 19th world congress on heart disease
  • Place of Presentation: Boston, USA
  • Year and Date: 2014-07-25 – 2014-07-28
• [Presentation] Branched-chain amino acids ameliorate heart failure in rats (2013)
  • Author(s): Tanada Y, Shioi T, Kawamoto A, Okuda J, Kimura T
  • Organizer: The 85th Scientific Sessions of American Heart Association
  • Place of Presentation: Dallas, USA
• [Presentation] Branched–chain amino acids prevent heart failure in rats (2013)
  • Author(s): Tanada Y, Shioi T, Kawamoto A, Okuda J, Kimura T
  • Organizer: Gordon Reseach Conferences, Biology of Aging
  • Place of Presentation: Lucca, Italy
• [Presentation] Tc-99m Sestamibi washout is a useful method to assess cardiac mitochondrial function and the increased risk of a failing heart: a translational approach to understand the metabolic state of the heart. (2012)
  • Author(s): Kato T, Shioi T, Kawamoto A, Kimura T, Nagakura D, Nakane E, Miyamoto S, Izumi T, Haruna T, Inoko T, Nohara R.
  • Organizer: The 84th Scientific Sessions of American Heart Association
  • Place of Presentation: Los Angeles, USA
• [Presentation] Abnormal liver metabolism and pro-inflammatory responses as modulators of cardiac cachexia in a rat model of heart failure. (2012)
  • Author(s): Kato T, Shioi T, Niizuma S, Kawashima T, Okuda J, Kawamoto A, Soga T, Kimura T.
  • Organizer: European Society of Cardiology Congress 2012.
  • Place of Presentation: Munich, Germany