Knockdown of FAF2 Prevents Alcohol-Induced Steatosis in Mouse Liver

Alcohol is metabolized in the liver, and chronic consumption can lead to inflammation, scarring, and damage to liver cells. The pathogenesis of alcoholic liver disease (ALD), a complicated condition, is characterized by a succession of histopathological alterations that occur through a multistep and multifactorial process. FAF2/UBXD8/ETEA is a ubiquitin ligase adaptor protein and plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. Recent GWAS study indicated that FAF2 was associated with ALD, but the exact function of FAF2 in ALD has not been identified yet. The objective of this study was to investigate the role of FAF2 in ALD.Our study revealed a noteworthy rise in hepatic FAF2 protein expression among individuals with ALD and mice subjected to chronic-plus-single binge ethanol feeding. The suppression of FAF2 in mice liver provided protection against alcohol-induced hepatic steatosis. Adeno-associated virus (AAV) subtype 8 carrying either scrambled shRNA (control) or FAF2-specific shRNA #3 was delivered into the livers of wild-type mice through tail vein injection. After 2 weeks, mice were fed with either control or ethanol-containing diet for 10 days, followed by a single binge of maltose (control) or ethanol .