The protection of fatty liver disease by fish-derived dietary habit targeted to intestinal bile acid control

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00904
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Fisheries Research and Education Agency
• Principal Investigator: Miyata Masaaki 国立研究開発法人水産研究・教育機構, 水産大学校, 教授 (90239418)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胆汁酸 / 消化管 / タウリン / 魚油 / 脂肪性肝疾患 / FXR

Outline of Final Research Achievements

Farnesoid X receptor (Fxr)-null mice were used as a model of fatty liver disease because they exhibit higher levels of hepatic lipids and hepatic damage-associated diagnostic markers. The feeding of 2% fish oil diet for four weeks decreased hepatic and serum lipid levels and hepatic damage-associated diagnostic marker levels in Fxr-null mice, compared to those of control diet. However, no significant differences in bile acid composition and content in intestinal lumen were observed between control and fish oil group.
The drinking of 0.5% taurine containing water for 4 weeks significantly decreased hepatic and serum lipid levels and hepatic damage-associated diagnostic marker levels in Fxr-null mice, compared to those of control group. Significant changes in bile acid composition and content in intestinal lumen of wild-type mice were found between 0.5% taurine and control group. mRNA levels of FXR target gene (Fgf15 and Shp) were significantly decreased in 0.5% taurine group.

Free Research Field

食品機能学

Academic Significance and Societal Importance of the Research Achievements

水産由来食品に多く含まれる魚油成分やタウリンの摂取が脂肪性肝疾患モデルマウスの病態を改善する事が示された。特にタウリンの処置においては、消化管管腔内の胆汁酸組成が変化し、胆汁酸量も増加することが示され、同時に消化管の胆汁酸受容体であるFXRシグナルを軽減する可能性が示された。これらの事実は消化管の胆汁酸組成を変化させることにより消化管FXRシグナルを調節することで、脂肪性肝疾患の予防や改善が出来る可能性を示している。胆汁酸組成変化を誘起出来る食品成分に脂肪性肝疾患の予防や改善作用がある可能性が考えられ、本研究は脂肪性肝疾患の予防や改善作用のある食品成分の探索のために重要な知見を提供した。