The differentially expressed proteins in WT liver tissues and FetA KO liver tissues of NIAAA model mice

To explore the potential role of FetA in AFLD, FetA KO mice were subjected to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) model for in vivo analysis. The liver protein in EtOH-fed FetA WT and KO mice was extracted. The protein of RAW data was identified and quantified by Proteome Discoverer2.5/Spectronaut16. The differentially expressed proteins in WT liver tissues and FetA KO liver tissues was identified by R/Bioconductor package limma v.3.24.15. Proteins with |Log2FC| ＞ 0.585 were included, and P < 0.05 was considered significant. R-base (v.3.4.3) is used to perform calculations and visualizations. In this study, we found that FetA knockout or knockdown significantly reduced hepatic lipid droplet accumulation, oxidative stress, and inflammation in AFLD mice. FetA deletion leads to increase of autophagy flux and results in decreased TLR4 protein levels, subsequently inhibiting the NF-kB signaling pathway and the formation of pro-inflammatory M1 macrophages and then reducing the release of inflammatory cytokines. In short, our study indicates that inhibition of FetA could help prevent or reverse the progression of AFLD, and the FetA-TLR4 axis may be a target for AFLD drug development.