Development of a novel treatment for nonalcoholic steatohepatitis by targeting small intestinal fatty acid transporters

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07982
• 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: Ehime University
• Principal Investigator: Yamamoto Yasunori 愛媛大学, 医学部附属病院, 講師 (20649066)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: NASH / 腸管脂肪酸吸収 / 選択的 PPARαモジュレーター / 肝線維化抑制 / pemafibrate

Outline of Final Research Achievements

The purpose of this study was to verify whether PPARα agonists, which control intestinal fatty acid transporters including intestinalMTP, suppress liver fibrosis in non-alcoholic steatohepatitis (NASH). NASH model rats fed a high-fat diet were divided into Pemafibrate (PPARα agonist) administration group and non-administration group, and lipid deposition in the small intestine and the expression of lipid metabolism-related genes, as well as liver fibrosis and α-SMA level, were evaluated. In the Pemafibrate-treated group, lipid droplet deposition in the intestinal tract was markedly reduced and the expression of lipid regulation-related molecules was suppressed compared to the non-treated group. In addition, improvement in liver fibrosis and decreased expression of fibrosis-related molecules were observed. PPARα agonists reduce liver fibrosis by inhibiting lipid droplet formation and absorption in the intestine, suggesting that they may serve as a new therapeutic target for NASH.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

【学術的意義】本研究は、NASHモデルラットにおいて、選択的PPARαモジュレーターであるpemafibrateが腸管での脂質吸収および肝線維化に及ぼす影響を明らかにした初めての研究である。本研究の結果は、NASHにおける腸管脂質吸収動態の調節が、肝線維化を予防する新たな治療戦略となる可能性を示唆している。
【社会的意義】NASHは肝硬変や肝細胞がんに進行し得る慢性疾患であり、その有病率は人口の3-5%と推計される。本研究で示されたpemafibrateによるNASHの腸管脂質吸収抑制と肝線維化軽減効果は、MASHの新たな治療選択肢となる可能性があり、患者の予後改善に寄与することが期待される。