Dysregulated hepatic lipid metabolism and gut microbiota associated with early-stage NAFLD in ASPP2-deficiency mice

作者：Fang Xie, Hangfei Xu, Jing Zhang, Xiao-ni Liu, Buxin Kou, Mengyin Cai, Jing Wu, Dong Jin-ling, Qinghua Meng, Yi Wang, Dexi Chen, Yang Zhang · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.974872 · 被引用次数：20 · 研究领域：Gut microbiota and health、Liver Disease Diagnosis and Treatment、Drug Transport and Resistance Mechanisms

Background Growing evidence indicates that lipid metabolism disorders and gut microbiota dysbiosis were related to the progression of non-alcoholic fatty liver disease (NAFLD). Apoptosis-stimulating p53 protein 2 (ASPP2) has been reported to protect against hepatocyte injury by regulating the lipid metabolism, but the mechanisms remain largely unknown. In this study, we investigate the effect of ASPP2 deficiency on NAFLD, lipid metabolism and gut microbiota using ASPP2 globally heterozygous knockout (ASPP2 +/- ) mice. Methods ASPP2 +/- Balb/c mice were fed with methionine and choline deficient diet for 3, 10 and 40 day to induce an early and later-stage of NAFLD, respectively. Fresh fecal samples were collected and followed by 16S rRNA sequencing. HPLC-MRM relative quantification analysis was used to identify changes in hepatic lipid profiles. The expression level of innate immunity-, lipid metabolism- and intestinal permeability-related genes were determined. A spearman’s rank correlation analysis was performed to identify possible correlation between hepatic medium and long-chain fatty acid and gut microbiota in ASPP2-deficiency mice. Results Compared with the WT control, ASPP2-deficiency mice developed moderate steatosis at day 10 and severe steatosis at day 40. The levels of hepatic long chain omega-3 fatty acid, eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3), were decreased at day 10 and increased at day 40 in ASPP +/- mice. Fecal microbiota analysi...