Novel therapeutic strategies for liver injury based on the hepatoprotective effects of n3 fatty acids and comprehensive analysis of lipid profiles

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08563
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Akita University
• Principal Investigator: morii mayako 秋田大学, 医学部附属病院, 助教 (10375280)
• Co-Investigator(Kenkyū-buntansha): 蛇口 琢 秋田大学, 医学系研究科, 助教 (20375281) ; 渡部 亮 秋田大学, 医学部附属病院, 医員 (80638255) ; 吉野 裕顕 秋田大学, 医学系研究科, 准教授 (90182807)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ω3系脂肪酸 / 肝硬変 / 腸管機能不全合併肝障害 / 短腸症候群

Outline of Final Research Achievements

In recent years, the efficacy of fish oil-derived fat emulsion in the treatment of liver disorders complicated by intestinal insufficiency has been reported, and the improvement of fatty hepatitis and liver fibrosis in clinical cases treated with this emulsion was reported, and using plasma from cases treated with the emulsion, 92 fatty acids and their metabolites were analysed and several fatty acid metabolites were found to be 4-10 times higher than in normal controls and were named Omegaven-induced-factors (OIFs). Furthermore, the expression of CIP7A1, the rate-limiting enzyme of bile acid metabolism, was markedly induced in primary cultured hepatocytes of mice treated with OIFs.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

魚油由来脂肪製剤の肝庇護に対する作用機序はいまだ不明の点も多い。魚油中に豊富に含まれるω3系脂肪酸の抗炎症作用が主な作用とされてきたが、投与された患児脂肪プロファイルは正常コントロールと著しく異なっており、未知の生理活性を持ちうる代謝産物が複数検出されている。これらの物質の肝細胞、類洞壁細胞、炎症細胞への作用を読み解くことによって肝障害に対する新たな治療戦略を確立したことは、本剤の適応や投与法の検討から臨床に直結し社会的意義のあることであり、また脂肪酸代謝産物の生物学的意義を明らかにしたことは学術的に極めて重要である。