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Apolipoprotein H deficiency exacerbates alcohol-induced liver injury via gut Dysbiosis and altered bile acid metabolism.
- Source :
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Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2024 Oct; Vol. 1869 (7), pp. 159535. Date of Electronic Publication: 2024 Jul 20. - Publication Year :
- 2024
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Abstract
- Background: APOH plays an essential role in lipid metabolism and the transport of lipids in the circulation. Previous studies have shown that APOH deficiency causes fatty liver and gut microbiota dysbiosis in mouse models. However, the role and potential mechanisms of APOH deficiency in the pathogenesis of alcoholic liver disease remain unclear.<br />Methods: C57BL/6 WT and ApoH <superscript>-/-</superscript> mice were used to construct the binge-on-chronic alcohol feeding model. Mouse liver transcriptome, targeted bile acid metabolome, and 16S gut bacterial taxa were assayed and analyzed. Open-source human liver transcriptome dataset was analyzed.<br />Results: ApoH <superscript>-/-</superscript> mice fed with alcohol showed severe hepatic steatosis. Liver RNAseq and RT-qPCR data indicated that APOH deficiency predominantly impacts hepatic lipid metabolism by disrupting de novo lipogenesis, cholesterol processing, and bile acid metabolism. A targeted bile acid metabolomics assay indicated significant changes in bile acid composition, including increased percentages of TCA in the liver and DCA in the gut of alcohol-fed ApoH <superscript>-/-</superscript> mice. The concentrations of CA, NorCA, and HCA in the liver were higher in ApoH <superscript>-/-</superscript> mice on an ethanol diet compared to the control mice (p < 0.05). Additionally, APOH deficiency altered the composition of gut flora, which correlated with changes in the liver bile acid composition in the ethanol-feeding mouse model. Finally, open-source transcript-level data from human ALD livers highlighted a remarkable link between APOH downregulation and steatohepatitis, as well as bile acid metabolism.<br />Conclusion: APOH deficiency aggravates alcohol induced hepatic steatosis through the disruption of gut microbiota homeostasis and bile acid metabolism in mice.<br />Competing Interests: Declaration of competing interest Yaming Liu has patent issued to Yaming Liu. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Humans
Male
Mice
Disease Models, Animal
Liver metabolism
Liver pathology
Mice, Inbred C57BL
Mice, Knockout
Bile Acids and Salts metabolism
Dysbiosis metabolism
Dysbiosis microbiology
Dysbiosis chemically induced
Gastrointestinal Microbiome
Lipid Metabolism
Liver Diseases, Alcoholic metabolism
Liver Diseases, Alcoholic microbiology
Liver Diseases, Alcoholic pathology
Liver Diseases, Alcoholic genetics
Liver Diseases, Alcoholic etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-2618
- Volume :
- 1869
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular and cell biology of lipids
- Publication Type :
- Academic Journal
- Accession number :
- 39033850
- Full Text :
- https://doi.org/10.1016/j.bbalip.2024.159535