The DEAD ‐box helicase DDX3x ameliorates non‐alcoholic fatty liver disease via mTORC1 signalling pathway

作者：Peihao Liu, Yuwei Zhang, Chenxi Tang, Cen Li, Yishu Chen, Sha Li, Xueyang Chen, Mengli Yu, Jie Zhang, Xiaofen Zhang, Hang Zeng, Chengfu Xu, Chaohui Yu · 发表于：Liver International · 年份：2022 · DOI：10.1111/liv.15278 · 被引用次数：7 · 研究领域：Liver Disease Diagnosis and Treatment、RNA Research and Splicing、Hepatitis C virus research

BACKGROUND & AIMS: The DEAD (Asp-Glu-Ala-Asp)-box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non-alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD. METHODS: DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno-associated virus-containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD. RESULTS: DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin-proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD-induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD-induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 s...