S100A11 Promotes Liver Steatosis via FOXO1-Mediated Autophagy and Lipogenesis

作者：Linqiang Zhang, Zhiguo Zhang, Chengbin Li, Tingting Zhu, Jing Gao, Hu Zhou, Yingzhuan Zheng, Qing Chang, Mingshan Wang, Jieyu Wu, Liyuan Ran, Yingjie Wu, Huilai Miao, Xiaoju Zou, Bin Liang · 发表于：Cellular and Molecular Gastroenterology and Hepatology · 年份：2020 · DOI：10.1016/j.jcmgh.2020.10.006 · 被引用次数：88 · 研究领域：S100 Proteins and Annexins、Autophagy in Disease and Therapy、GDF15 and Related Biomarkers

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is becoming a severe liver disorder worldwide. Autophagy plays a critical role in liver steatosis. However, the role of autophagy in NAFLD remains exclusive and under debate. In this study, we investigated the role of S100 calcium binding protein A11 (S100A11) in the pathogenesis of hepatic steatosis. METHODS: We performed liver proteomics in a well-established tree shrew model of NAFLD. The expression of S100A11 in different models of NAFLD was detected by Western blot and/or quantitative polymerase chain reaction. Liver S100A11 overexpression mice were generated by injecting a recombinant adenovirus gene transfer vector through the tail vein and then induced by a high-fat and high-cholesterol diet. Cell lines with S100a11 stable overexpression were established with a recombinant lentiviral vector. The lipid content was measured with either Bodipy staining, Oil Red O staining, gas chromatography, or a triglyceride kit. The autophagy and lipogenesis were detected in vitro and in vivo by Western blot and quantitative polymerase chain reaction. The functions of Sirtuin 1, histone deacetylase 6 (HDAC6), and FOXO1 were inhibited by specific inhibitors. The interactions between related proteins were analyzed by a co-immunoprecipitation assay and immunofluorescence analysis. RESULTS: The expression of S100A11 was up-regulated significantly in a time-dependent manner in the tree shrew model of NAFLD. S100A11 expression was ...