Suppression of non-alcoholic steatohepatitis by ubiquitin ligases in mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K12901
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Abe Tomoki 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (00736605)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 非アルコール性脂肪肝炎 / ユビキチンリガーゼ / Cbl-b / マクロファージ

Outline of Final Research Achievements

In this study, we aimed to elucidate molecular mechanisms for non-alcoholic steatohepatitis by using mouse models. We found that knockout of Cbl-b promoted lipid accumulation and inflammation in livers of mice fed high-fat diet. In wild-type mice, high-fat diet increased hepatic protein expression levels of Cbl-b. We also used mice fed high-fat high-sucrose diet during sleep phase as novel model of fatty liver. Feeding during sleep phase induced obesity and hepatic lipid accumulation in mice, compared with ad libitum feeding. We found that feeding during sleep phase influenced on expression of several ubiquitin ligases, which may be associated with non-alcoholic steatohepatitis in livers of mice. Further research is needed to elucidate the roles of these ubiquitin ligases in diet-induced fatty liver and non-alcoholic steatohepatitis.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

NASHは肝硬変や肝がんの発症を介して生命を脅かす重篤な疾患にもかかわらず、有効な治療薬はいまだにない。それは、NASHの発症メカニズムには不明な点が多く残っているためである。本研究ではユビキチンリガーゼという酵素に着目し、NASHの発症メカニズムの解明を目指した。