Pathophysiological mechanisms of age-related exacerbation of steatohepatitis and skeletal muscle atrophy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17032
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Juntendo University
• Principal Investigator: Ishizuka Kei 順天堂大学, 医学部, 非常勤助教 (70870327)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 非アルコール性脂肪肝炎 / 加齢 / 脂質代謝 / サルコペニア（筋萎縮）

Outline of Final Research Achievements

To clarify the relationship between age-related muscle loss (sarcopenia) and nonalcoholic steatohepatitis, we investigated the effects of aging on the responsiveness of liver and skeletal muscle to a high-fat diet using aged mice. Our findings demonstrated that imbalances in lipid metabolism in liver, quantitative/qualitative changes in hepatic lipids and exacerbation of lipotoxicity contribute to the development of steatohepatitis in aged mice fed a high-fat diet. Additionally, they clearly suggested that changes in IGF-1 and hepatokine expression in liver promote inflammation and ubiquitination in skeletal muscle tissue.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究は加齢性筋萎縮と非アルコール性脂肪肝炎との病態関連を明らかにするために肝筋連関に着目した。これまでに当研究室で行ってきた肝の脂質代謝・ストレス応答に関する研究の蓄積と、骨格筋萎縮との関連を活かした独創的なものである。本研究での成果により、NASHの予防・新規治療法だけでなく高齢に伴う筋萎縮の軽減にも繋がることが期待できる。