Elucidation of new metabolism promotion mechanism through extracellular vesicles derived from skeletal muscle

• Project/Area Number: 17K01843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Mie University
• Principal Investigator: Kobayashi Yoshinao 三重大学, 保健管理センター, 教授 (70378298)
• Co-Investigator(Kenkyū-buntansha): 江口 暁子 三重大学, 医学系研究科, 特任講師(研究担当) (00598980)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 細胞外小胞 / メタボリック症候群 / 運動 / プロテオミクス解析 / 運動負荷 / 骨格筋 / 運動量 / 骨格筋量 / 中性脂肪 / 社会医学 / 内科

Outline of Final Research Achievements

We explored the association between circulating extracellular vesicles (EVs) level and various metabolic parameters, including obesity and lipid and glucose metabolisms, among 203 subjects with or without risk factor for metabolic diseases. Circulating EV number was significantly higher in men than in women. Circulating EV number correlated most strongly and significantly with elevated triglyceride. Circulating EVs represent a promising metabolic biomarker for lipid and glucose metabolism and have potential for monitoring metabolic status in humans, including individuals without metabolic risk factors.
In addition, we revealed that high intensity intermittent training exercise (HIIT-Ex) significantly influenced circulating EV number along with pulse rate, BP, and catabolism of skeletal muscle. Furthermore, HIIT-Ex promoted changes in EV protein composition, indicating that EVs intercommunicate across various organs in response to HIIT-Ex.

Academic Significance and Societal Importance of the Research Achievements

血液中の細胞外小胞の数および成分は、メタボリック症候群における全身の代謝異常を反映することが明らかになり、その時の健康状態を評価するための指標（バイオマーカー）になることが示された。
運動により血液中の細胞外小胞の数と構成タンパク質が変化することが明らかになり、構成タンパク成分の変化を通して運動により引き起こされる生体内の様々な代謝調節反応を評価することができ、健康増進に必要な運動の設定に役立つ情報が得られることが示された。

Research Products

• [Journal Article] Circulating extracellular vesicles are associated with lipid and insulin metabolism (2018)
  • Author(s): Yoshinao Kobayashi, Akiko Eguchi, Mina Tenpaku, Tatsuro Honda, Kenji Togashi, Motoh Iwasa et al.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 315 Issue: 4 Pages: E574-E582
  • DOI: 10.1152/ajpendo.00160.2018
  • Peer Reviewed
• [Presentation] 非アルコール性肝炎に関連するメタボリックリスク因子の上昇により肝細胞や脂肪細胞由来のExtracellular vesicle数が増加する (2019)
  • Author(s): 江口暁子、小林由直、天白美奈、岩佐元雄、竹井謙之
  • Organizer: 第9回肥満と消化器疾患研究会
• [Presentation] Association among serum bile acids, liver fibrosis and skeletal muscle volume in NAFLD and biological effects of bile acids on skeletal muscle (2019)
  • Author(s): Yoshinao Kobayashi, Yasuyuki Tamai, Akiko Eguchi, Mina Tenpaku, Ryota Shigefuku, Motoh Iwasa, Yoshiyuki Takei
  • Organizer: Annual meeting of American Association for the Study of the Liver 2019
  • Int'l Joint Research
• [Presentation] Changes in serum bile acids concentrations and components associated with reduced skeletal muscle volume in NAFLD (2018)
  • Author(s): Yoshinao Kobayashi, Yasumasa Tamai, Akiko Eguchi, Motoh Iwasa, Yoshiyuki Takei
  • Organizer: Annual meeting of American Association for the Study of Liver disease (AASLD)
  • Int'l Joint Research