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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06244
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Niigata 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
• Keywords: 心不全 / 老化促進代謝物質 / 加齢同期

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.

Free Research Field

循環器

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。