Mechanisms of nonalcoholic fatty liver disease using a diet-induced mouse model of fatty liver during pregnancy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11063
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokushima Bunri University
• Principal Investigator: Kawakami Takashige 徳島文理大学, 薬学部, 講師 (40441589)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 脂肪肝 / ビザンチン / 妊娠マウス / 小胞体ストレス

Outline of Final Research Achievements

We attempted to elucidate the molecular mechanisms of fatty liver using a diet-induced fatty liver pregnant mouse model, and investigated Vizantin which is a potential drug for treatment of fatty liver and obesity. When pregnant mice were fed a fatty liver-induced diet (CDAA), marked fatty liver and liver fibrosis were observed. Further, we used a ER stress inhibitor 4-phenylbutyrate (PBA) to test whether fatty liver induced by a CDAA diet was mediated by ER stress in pregnant mice. The results showed that PBA ameliorated fatty liver development in CDAA-fed pregnant mice, suggesting that ER stress is, at least in part, responsible for diet-induced fatty liver during pregnancy. Metabolomic analysis revealed that acylcarnitines were significantly reduced in plasma of CDAA-fed pregnant mice compared to control mice. Vizantin suppressed fatty liver and improved adipocyte function. The results of this study suggested that Vizantin could be a candidate for a new drug for fatty liver.

Free Research Field

環境衛生学

Academic Significance and Societal Importance of the Research Achievements

生活習慣の変化に伴い、肝がん・肝硬変の原因となる肥満・脂肪肝の発症人口が増加している。健康的な生活を担保し、医療費の抑制のためにその予防と治療が喫緊の課題である。本研究では脂肪肝発症モデルとして妊娠マウスを用い、極めて短期間で脂肪肝を生じるモデル動物であることを見出した。本実験モデルは、これまで原因が未詳である急性妊娠脂肪肝のモデル動物となることも予想され、脂肪肝発症に関わる因子を明らかにした点と合わせて学術的意義がある。また、大学の研究室から創生された新規化合物が脂肪肝を抑制することを見出し、脂肪肝の新たな解決方法とした点において社会的意義は高いと考えられる。