Department of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, 361001, Fujian Province, China.
Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, 361001, Fujian Province, China.
Lipids Health Dis. 2022 Sep 19;21(1):89. doi: 10.1186/s12944-022-01699-7.
Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis.
ApoH mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes.
ApoH mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation-reduction process between in alcohol-fed ApoH mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P < 0.05). Moreover, KEGG enrichment analysis, using PICRUSt software, revealed that metabolic functions were activated in the gut microorganisms of ApoH mice with ethanol feeding (P < 0.05).
Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.
酒精性肝病（ALD）是一种由过量饮酒和滥用引起的主要慢性肝病。载脂蛋白 H（APOH）参与脂质代谢，可能在 ALD 中有潜在的调节作用。因此，本研究旨在探讨 ApoH 对酒精性肝损伤和肠道微生物失调的影响。
构建了 ApoH 敲除小鼠，并构建了协同性酒精性脂肪性肝炎小鼠模型，以评估肝功能和病理变化。
ApoH 敲除小鼠表现出自发性脂肪性肝炎。酒精喂养的 WT 和 ApoH 小鼠均出现严重的肝脂肪变性，酒精摄入后 ApoH 表达降低。此外，RNA-seq 和 KEGG 通路分析表明，酒精喂养的 ApoH 小鼠与配对喂养的对照组小鼠之间差异表达基因富集在脂质代谢和氧化还原过程中。最后，通过 16S rRNA Illumina 下一代测序评估肠道微生物多样性和组成。与酒精喂养的 WT 小鼠和所有对照喂养的小鼠相比，酒精喂养的 ApoH 小鼠的肠杆菌属的 alpha 多样性较低（P < 0.05）。此外，使用 PICRUSt 软件进行的 KEGG 富集分析表明，酒精喂养的 ApoH 小鼠的肠道微生物中代谢功能被激活（P < 0.05）。
酒精下调 ApoH 的表达，导致脂肪肝疾病和肠道微生物失调的进展。
