The circadian clock maintains cardiac function by regulating mitochondrial metabolism in mice

• Project/Area Number: 25460316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Wakayama Medical University
• Principal Investigator: Kohsaka Akira 和歌山県立医科大学, 医学部, 准教授 (00458051)
• Co-Investigator(Kenkyū-buntansha): Waki Hidefumi 順天堂大学, スポーツ健康科学部, 准教授 (50274957) ; Gouraud Sabine お茶の水女子大学, 理学部, 研究員 (30453179) ; Otsuka Tsuyoshi 和歌山県立医科大学, 医学部, 学内助教 (60760395)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 心不全 / 時計遺伝子 / ミトコンドリア

Outline of Final Research Achievements

Dysfunction of the circadian system has been shown to induce a malfunction of many organs including the heart. However, little is known about how the circadian clock regulates heart function. In the present study, we found that a heart-specific knockout of Bmal1, a core circadian clock gene, leads to age-dependent cardiomyopathy in mice. DNA microarray analysis revealed that expression levels of genes controlling energy metabolism such as mitochondrial biogenesis and ATP production are altered in the heart tissue of knockout animals. In addition, both function and morphology of mitochondria in cardiomyocytes are disrupted in heart-specific Bmal1 knockout mice. Together, our results indicate that the circadian clock in the heart plays an important role in regulating mitochondrial energetics, and thereby maintains heart function in mammals.

Research Products

• [Journal Article] The circadian clock maintains cardiac function by regulating mitochondrial metabolism in mice (2014)
  • Author(s): Kohsaka A, Das P, Hashimoto I, Nakao T, Deguchi Y, Gouraud SS, Waki H, Muragaki Y, Maeda M
  • Journal Title: PLOS ONE Volume: 9 Issue: 11 Pages: e112811-e112811
  • DOI: 10.1371/journal.pone.0112811
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Heart-specific disruption of Bmal1 leads to age-dependent hyperglycemia in mice (2016)
  • Author(s): Tomomi Nakao, Akira Kohsaka, Tsuyoshi Otsuka, Hue Thi Le, Masanobu Maeda
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] The clock, mitochondria, and heart function (2016)
  • Author(s): Akira Kohsaka, Masanobu Maeda
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
  • Invited
• [Presentation] Effects of heart-specific disruption of the circadian clock on systemic glucose metabolism in mice (2015)
  • Author(s): Akira Kohsaka, Tomomi Nakao, Tsuyoshi Otsuka, Hue Thi Le, Masanobu Maeda
  • Organizer: 8th FAOPS Congress
  • Place of Presentation: Bangkok
  • Year and Date: 2015-11-22
  • Int'l Joint Research
• [Presentation] マウス心筋の体内時計異常はインスリン抵抗性を引き起こす (2015)
  • Author(s): 向阪 彰、中尾友美、大塚剛司、レ ティ フォエ、前田正信
  • Organizer: 第51回高血圧関連疾患モデル学会学術総会
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2015-10-30
• [Presentation] 心臓の分子時計異常が与える全身の糖代謝調節への影響 (2015)
  • Author(s): 中尾友美、向阪 彰、大塚剛司、レ ティ フォエ、前田正信
  • Organizer: 第108回近畿生理学談話会
  • Place of Presentation: 近畿大学東大阪キャンパス 39号館
  • Year and Date: 2015-10-24
• [Presentation] 心臓の時計遺伝子機能と耐糖能異常の関係 (2015)
  • Author(s): 向阪 彰、中尾友美、グホ サビン、和気秀文、前田正信
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオータニ東京
  • Year and Date: 2015-04-23
• [Presentation] Insulin resistance in heart-specific Bmal1 knockout mice (2015)
  • Author(s): Tomomi Nakao, Akira Kohsaka, Mariko Kitauchi, Hikaru Ogata, Sabine S Gouraud, Hidefumi Waki, Masanobu Maeda
  • Organizer: 第92回日本生理学会大会・第120回日本解剖学会学術総会合同大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 糖尿病発症における心臓の時計遺伝子の関与について (2014)
  • Author(s): 中尾友美、向阪 彰、北内真理子、小形 光、グホ サビン、和気秀文、前田正信
  • Organizer: 第107回近畿生理学談話会
  • Place of Presentation: 兵庫医療大学 M講義室
  • Year and Date: 2014-10-25
• [Presentation] 体内時計による心機能制御 (2014)
  • Author(s): 向阪 彰、前田正信
  • Organizer: 第71回和歌山内分泌代謝研究会
  • Place of Presentation: 和歌山県立医科大学 生涯研修・地域医療センター
  • Year and Date: 2014-09-04
• [Presentation] 概日時計は心筋ミトコンドリア機能および心機能維持に関与する (2014)
  • Author(s): 向阪 彰、橋本いずみ、ダス パルタ、中尾友美、グホ サビン、和気秀文、村垣泰光、前田正信
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場、福岡サンパレス
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 心血管機能調節における生体リズムの重要性 (2014)
  • Author(s): 向阪 彰、前田正信
  • Organizer: 第17回日本病態栄養学会年次学術集会
  • Place of Presentation: 大阪国際会議場
• [Presentation] Circadian desynchronization disrupts heart mitochondrial metabolism in mice (2014)
  • Author(s): Izumi Hashimoto, Akira Kohsaka, Partha Das, Tomomi Nakao, Sabine S Gouraud, Hidefumi Waki, Masanobu Maeda
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学郡元キャンパス
• [Presentation] 生体リズムの異常が心機能に及ぼす影響の解析
  • Author(s): 橋本いずみ、向阪 彰、ダス パルタ、中尾友美、グホ サビン、和気秀文、村垣泰光、前田正信
  • Organizer: 第106回近畿生理学談話会
  • Place of Presentation: 奈良県立医科大学 基礎医学校舎1階