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- Title
Alcohol-dependent downregulation of apolipoprotein H exacerbates fatty liver and gut microbiota dysbiosis in mice.
- Authors
Liu, Yaming; Wu, Zhe; Zhang, Yong; Chen, Binbin; Yu, Shuqi; Li, Wanyun; Ren, Jianlin
- Abstract
Background: 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. Methods: ApoH−/− mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes. Results: 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). Conclusions: Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.
- Subjects
GUT microbiome; FATTY liver; DYSBIOSIS; PATHOLOGICAL physiology; MICE; ALCOHOL
- Publication
Lipids in Health & Disease, 2022, Vol 21, Issue 1, p1
- ISSN
1476-511X
- Publication type
Article
- DOI
10.1186/s12944-022-01699-7