The roles of branched chain amino acids released from liver endothelial cells in NAFLD and glucose intolerance.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08585
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Showa University
• Principal Investigator: MIYAZAKI AKIRA 昭和大学, 医学部, 教授 (70253721)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: カルパイン / NAFLD / 分枝アミノ酸

Outline of Final Research Achievements

Nonalcoholic fatty liver disease (NAFLD) induced by over eating is an important disease that leads to liver cirrhosis and liver cancer. However, efficient treatment except lifestyle improvement has been established. The current study elucidated that branched chain amino acids released from liver endothelial cells neighboring hepatocytes by the action of calpain protease expressed in liver endothelial cells are taken up by hepatocytes and accelerate lipid accumulation in liver. Base on this novel finding, we propose a novel therapeutic strategy for treatment of NAFLD by targeting calpain and/or a series of signal transduction induced by released branched chain amino acids by calpain action.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝障害(NAFLD)は肝硬変や肝がんの誘因となる重要な疾患であるが、生活習慣の改善以外に有効な治療法が確立されていない。本研究は、肝細胞に隣接する肝血管内皮細胞に発現するタンパク分解酵素、カルパインのはたらきにより、分枝アミノ酸が遊離して肝細胞に取り込まれ、脂肪蓄積を促進することを明らかにした。この新知見に基づき、カルパインやそれによって遊離する分枝アミノ酸に由来する一連のシグナルを標的とした新たな薬剤の開発を目指すNAFLD治療戦略の構築が可能になった。