Involvement of 12alpha-hydroxylated bile acids in the onset and aggravation of fatty liver

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H02900
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Hokkaido University
• Principal Investigator: ISHIZUKA Satoshi 北海道大学, 農学研究院, 教授 (00271627)
• Co-Investigator(Kenkyū-buntansha): 相沢 智康 北海道大学, 先端生命科学研究院, 教授 (40333596)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 胆汁酸

Outline of Final Research Achievements

Fatty liver is associated with development of noncommunicable diseases. inflammation and fibrosis occur based on lipid accumulation in the development of fatty liver. Although a high-fat-fed experimental animals are a well-known fatty liver model, those animals frequently have both lipid accumulation and inflammation in the liver, and no reasonable model is reported to separate lipid accumulation and inflammation with fibrosis. We observed an enhancement of secretion of 12α-hydroxylated bile acids from the liver in response to dietary energy and those bile acids induces liver lipid accumulation without inflammation and fibrosis. Also, induction of inflammation was found to aggravate the symptom substantially. This can be used as a presymptomatic model of fatty liver.

Free Research Field

食品栄養学

Academic Significance and Societal Importance of the Research Achievements

脂肪肝の発症モデルとして、炎症・繊維化を伴わない肝臓での脂質蓄積のみを呈するモデルを見出したことと、炎症を強制的に誘導させたときにはその症状が悪化するという単なる脂質蓄積に留まらない点を見出したことに学術的な意義があると考えられる。また、このモデルでは食事からのエネルギー摂取は通常のままで、肥満症状にはならない。健康診断などで見た目は肥満でなくても肝臓脂肪の蓄積が見られるヒトのモデルと考えることもでき、その後に起こりうる多様な疾患の予防において重要な観点を提示できた点は大きな成果と考えられる。