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Brown adipose tissue dysfunction promotes metabolic disorder in a failing heart.

Research Project

Project/Area Number 16H06244
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Cardiovascular medicine
Research InstitutionNiigata University

Principal Investigator

Shimizu Ippei  新潟大学, 医歯学総合研究科, 特任准教授 (60444056)

Research Collaborator Minamino Tohru  
Yoshida Yohko  
Soga Tomoyoshi  
Minokoshi Yasuhiko  
Okuda Shujiro  
Sakimura Kenji  
Sasaoka Toshikuni  
Walsh Kenneth  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords心不全 / 老化促進代謝物質 / 加齢同期 / ミトコンドリア / 褐色脂肪 / 代謝的リモデリング / メタボローム / コリン
Outline of Final Research Achievements

Brown adipose tissue (BAT) was initially characterized as an organ involved in thermogenic response, and studies suggest that BAT has crucial roles for the maintenance of systemic metabolic health. In this study, we tried to show the role of BAT in heart failure. TAC operation led to a significant reduction both in intraperitoneal and subcutaneous temperature. TUNEL-positive cells significantly increased in BAT during left ventricular (LV)-pressure overload. Gain of BAT function model improved thermogenesis and ameliorated cardiac dysfunction in TAC. In contrast, genetic model of BAT dysfunction promoted cardiac dysfunction. Metabolomic analyses showed that BAT dysfunction led to an increase in circulating choline level, and an increase in oxidized choline promoted metabolic dysfunction in the failing heart. Maintenance of BAT homeostasis and suppression of oxidized choline would become a novel therapeutic target for heart failure.

Academic Significance and Societal Importance of the Research Achievements

老化のプロセスは未だ謎が多く存在するが、様々な特性を有した臓器が、ほぼ同じ時相で加齢に伴う機能低下をきたす分子機序は、現在わかっている事実からは説明することができない。血管は酸素及び代謝物質を送達し、臓器の恒常性維持に不可欠な要素である。血液中に存在する何らかの分子や代謝物質が加齢同期の中心的役割を担い、かつ、老化に伴う病的側面を促進している可能性、が想定される。私はこのような役割を担う代謝物質を「老化促進代謝物質」と捉え、「加齢同期」の中心的役割を担うという仮説を検討したいと考えている。本研究課題にて同定された酸化型コリンは老化促進代謝物質の側面を有し、さらなる検討が必要である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (9 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Presentation (8 results) (of which Invited: 2 results)

  • [Int'l Joint Research] Kenneth Walsh/Virgenia大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Presentation] Disoriented choline metabolism promotes metabolic disorder in the failing heart2019

    • Author(s)
      清水逸平
    • Organizer
      第83回日本循環器学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心不全における、心筋・代謝的リモデリングの意義2018

    • Author(s)
      清水逸平
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
  • [Presentation] 加齢性疾患における褐色脂肪不全の意義2018

    • Author(s)
      清水逸平
    • Organizer
      糖尿病学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心不全、肥満における褐色脂肪不全の意義2018

    • Author(s)
      清水逸平
    • Organizer
      第23回アディポサイエンスシンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心不全、肥満における褐色脂肪不全の意義2018

    • Author(s)
      清水逸平
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Roles of aging signaling and disoriented choline metabolism in the failing heart2018

    • Author(s)
      清水逸平
    • Organizer
      International Society for Heart Research(ISHR)日本部会総会2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 老化疾患における褐色脂肪不全の意義2017

    • Author(s)
      清水逸平
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 心血管代謝疾患における脂肪不全の意義2017

    • Author(s)
      清水逸平
    • Organizer
      日本心血管内分泌代謝学会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2024-12-25  

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