The role of macrophages in the progression of fibrosis of NASH and its regulation by nutritional factors

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K19676
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: The University of Tokushima
• Principal Investigator: SHIMIZU Mayuko 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (20759021)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: NASH / 線維化 / 可視化 / リン脂質 / 病態特異的マクロファージ / ベルベリン / コレステロール / コール酸

Outline of Final Research Achievements

This study hypothesized that macrophage control inhibits the progression to fibrosis in non-alcoholic steatohepatitis. In a novel animal model of NASH fibrosis (iHFC-A/J mice), macrophage recruitment to the liver was increased with disease progression. After phagocytosed lipids, aggregated and activated, macrophages interacted with the surrounding fibroblasts, resulting in fibrosis progression, which was visualized histologically in the mouse model. Using this model, it was possible to evaluate that berberine suppresses macrophage aggregation and fibrogenesis. Because I demonstrated that berberine did not promote hepatic lipid efflux,it was suggested that berberine may directly regulate macrophages. This study indicated the usefulness of macrophage regulation in suppressing the onset of fibrosis in NASH.

Free Research Field

栄養学、病理学

Academic Significance and Societal Importance of the Research Achievements

ステージ2以上の高度な線維化には肝線維化特効薬による処置がまず必要ではあるものの、生活習慣に端を発するNASHのような疾患は原因を取り除かない限り同様の病態が再発する可能性は高い。本研究はマクロファージ不活化を介した治療法の開発でなく、マクロファージを活性化する特定の脂質を明らかにし、NASH線維化の予防あるいは再発防止につなげ、最終的に肝線維化の根治を目指すためのエビデンスになると考えられる。