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

2015 Fiscal Year Final Research Report

• 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
• 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.

Free Research Field

循環生理学、時間生物学、内分泌代謝学