Identification of ceramide molecular species contributing to exacerbation of NAFLD and elucidation of its action

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K12905
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Kyoto Prefectural University
• Principal Investigator: Kobayashi Keiko 京都府立大学, 生命環境科学研究科, 助手 (50611117)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: セラミド代謝 / 脂質代謝 / NAFLD

Outline of Final Research Achievements

Nonalcoholic fatty liver disease (NAFLD) is caused by an imbalance in hepatic lipid homeostasis and hepatic fat accumulation. Some fatty livers develop inflammation that progresses to cirrhosis. Ceramide is known as an apoptotic lipid mediator and we identified that increasing ceramide affects diabetes and atherosclerosis exacerbation. In this study, we examined the relationship between fibrosis development and ceramide metabolism. Administration of high fat, high cholesterol and cholic acid diet to Sprague Dawley rat revealed that specific ceramide species increased significantly in high leveled fibrosis even though the total ceramide concentration did not significantly.

Free Research Field

栄養学

Academic Significance and Societal Importance of the Research Achievements

本研究は、「生理活性脂質セラミドは分子種の違いによりその作用が異なる」という独自の視点から、NAFLDの増悪機構の探索を試みた。結果、NASH以降段階においてC18:0およびC24:1セラミドの分子種が優位に増加することを初めて明らかにした。これらの研究を通して得た知見から、特定のセラミド分子種の生成に関わる酵素を明らかにし、これを阻害することで、NAFLDの病態増悪の予防に貢献できると考えている。