Elucidation of the pathological mechanism of obesity-related liver cancer and development of the new treatment methods, focusing on secretory factors from hepatic stellate cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07924
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: National Defense Medical College
• Principal Investigator: Tomita Kengo 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 病院 内科, 准教授 (50317129)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 非アルコール性脂肪肝炎 / 肝臓がん / 肝線維化 / 肝星細胞 / lipoprotein lipase

Outline of Final Research Achievements

In patients with nonalcoholic steatohepatitis (NASH), increased secretion of lipoprotein lipase (LPL) was observed specifically in hepatic stellate cells (HSCs). The increase in serum obesity-related factors, associated with NASH, promoted LPL secretion in HSCs. LPL enhanced cholesterol uptake from serum lipoproteins into HSCs and promoted free cholesterol accumulation in HSCs, resulting in activation of HSCs via TLR4 signal enhancement and progression of liver fibrosis in NASH. These results also suggest that LPL could be involved in the pathophysiology of obesity-related liver cancer.

Free Research Field

脂肪肝炎、肝がん

Academic Significance and Societal Importance of the Research Achievements

NASHの患者数は本邦で300万人にも達するとされているものの、未だ確立された治療法が存在しない。本研究により、肝星細胞由来の分泌因子LPL がNASH肝線維化を進展させることが明らかとなった。今後LPLを標的とすることにより、患者数の多いNASHおよびそれに伴う肥満関連肝がんの新たな治療法を確立できる可能性が高く、本研究成果の学術的・社会的意義は大きい。