Suppression of non-alcoholic steatohepatitis by ubiquitin ligases in mice

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• 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 / NASH / 脂肪肝 / 食事性脂肪肝

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.

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。

Research Products

• [Journal Article] Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice. (2020)
  • Author(s): Abe T, Yamamoto S, Konishi T, Takahashi Y, Oishi K.
  • Journal Title: Nutr Res . Volume: 82 Pages: 34-43
  • DOI: 10.1016/j.nutres.2020.07.003
  • Peer Reviewed
• [Journal Article] Food deprivation during active phase induces skeletal muscle atrophy via IGF-1 reduction in mice. (2019)
  • Author(s): Abe T, Kazama R, Okauchi H, Oishi K.
  • Journal Title: Arch Biochem Biophys. Volume: 677 Pages: 108160-108160
  • DOI: 10.1016/j.abb.2019.108160
  • Peer Reviewed
• [Presentation] 摂食のタイミングの乱れはIGF-1の減少を介して骨格筋を萎縮させる (2020)
  • Author(s): 安倍知紀、大石勝隆
  • Organizer: 第74回日本栄養・食糧学会大会
• [Presentation] 食餌時刻の乱れがマウス骨格筋に与える影響 (2020)
  • Author(s): 安倍知紀
  • Organizer: 第67回日本栄養改善学会学術総会
• [Presentation] Food deprivation during active phase induces skeletal muscle atrophy in mice (2020)
  • Author(s): Tomoki Abe, Katsutaka Oishi
  • Organizer: 第43回日本分子生物学会年会
  • Invited
• [Presentation] 摂食タイミングの乱れは骨格筋を萎縮させる (2019)
  • Author(s): 安倍知紀、風間玲、大石勝隆
  • Organizer: 第73回日本栄養・食糧学会大会
• [Presentation] 非活動期の時間制限給餌による脂肪組織の肥大化メカニズム (2018)
  • Author(s): 安倍知紀、風間玲、大石勝隆
  • Organizer: 第5回時間栄養科学研究会
• [Presentation] 活動リズムに同期したインスリンの分泌リズムが骨格筋量の維持に重要である (2018)
  • Author(s): 安倍知紀、風間玲、大石勝隆
  • Organizer: 第25回時間生物学会学術大会
• [Presentation] 非活動期の時間制限給餌による脂肪組織の肥大化メカニズム (2018)
  • Author(s): 安倍知紀、風間玲、大石勝隆
  • Organizer: 第13回環境生理学プレコングレス