Elucidation of the molecular mechanism of muscle insulin resistance induced by physical inactivity and establishment of prevention method.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K01729
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: KAKEHI saori 順天堂大学, 医学(系)研究科(研究院), 特任助教 (00450560)
• Co-Investigator(Kenkyū-buntansha): 桜庭 景植 順天堂大学, スポーツ健康科学部, 教授 (50175460)
• Co-Investigator(Renkei-kenkyūsha): TAMURA Yoshifumi 順天堂大学, 医学部, 准教授 (80420834)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 不活動 / 骨格筋 / インスリン感受性 / 細胞内脂質

Outline of Final Research Achievements

Physical inactivity (PI) has been shown to impair muscle insulin sensitivity (M-IS); however, its mechanisms have not been elucidated yet. To elucidate them, we used 24h hind-limb cast immobilization (HCI) for PI model in mice. We found that 24h HCI increased intramyocellular diacylglycerol (IMDG), while IM triacylglycerol (TG) was not changed. In parallel with IMDG accumulation, M-IS and insulin signaling were reciprocally impaired. The IMDG accumulations were also accompanied by increased expression level and activity of Lipin1, an enzyme converting phosphatidate to DG. The HCI induced IMDG accumulation and impaired M-IS in soleus muscle were prevented by dominant negative Lipin1 overexpression in the muscle. Finally, we found the possibility that 24h HCI in human also induce IMDG accumulation and Lipin1 expression. These results suggested that 24h HCI increase IMDG and decrease M-IS. Increased Lipin1 activity is at least partly involved in the mechanisms.

Free Research Field

運動科学