Transcriptomic analysis of fatty liver induced by alcohol and high-fat diet
Objective To induce a mouse model of fatty liver through alcohol gavage and high-fat diet,observe the hepatic phenotype and transcriptomic changes,analyze the hepatotoxic effects of alcohol,high-fat diet,and their combinations.Methods Mice were divided into control group(PBS),high-fat diet group(high-fat feed),alcohol gavage group(40%alcohol),and combined diet group(alcohol+high-fat feed).HE staining was used to observe the pathological morphology of liver tissues in each group of mice.Liver RNA was extracted for tran-scriptome sequencing,and the changes in transcriptome profiles of each group were analyzed to observe the effects on the liver under the influence of a single risk factor and dual risk factors.A gene expression regulatory network was constructed to identify core genes in the network and validate them.Results At the pathological level,the combined diet group showed more severe lipid accumulation and inflammation in the liver compared to the groups with single risk factors.Transcriptome analysis results revealed that the gene expression in the combined diet group exhibited a more prominent activation of lipid accumulation pathways and a tendency towards deterioration compared to the groups with a high-fat diet alone and alcohol gavage.By intersecting the differentially expressed genes between single and double risk factor groups,key risk genes leading to liver damage in fatty liver were i-dentified.Functional analysis results indicated that the gene expression changes in the mouse liver under high-fat alcohol conditions not only involved abnormalities in fat metabolism but also were associated with adverse drug metabolism,ultimately leading to increased liver inflammation.Network analysis identified Acacb,Cyp2b10,and Cd36 as potential key targets of gene expression changes in the liver of the high-fat diet group.Conclusion The findings of this study indicate that while both alcohol consumption and a high-fat diet contribute to fatty liver through lipid accumulation,the impact on the liver is not identical.Individuals on a high-fat diet may experience more severe liver effects when consuming alcohol.Further in-depth exploration is required to elucidate the specif-ic mechanisms underlying the combined effects of high-fat diet and alcohol consumption on the liver.
国家科技期刊平台
NSTL
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