pAAV-ZsGreen-shRNA

Chronic alcohol consumption induces hepatic lipid accumulation, oxidative stress, and inflammation, contributing to alcohol-associated liver disease (ALD). The researchers investigated the role of the ubiquitin ligase adaptor FAF2 in ALD pathogenesis. Using liver-specific knockdown via adeno-associated virus serotype 8 (AAV8) carrying Creative Biogene's pAAV-ZsGreen-FAF2-shRNA, they demonstrated that suppression of FAF2 mitigates ethanol-induced liver steatosis in mice. Transcriptomic analyses revealed that FAF2 knockdown altered expression of lipid metabolism genes regulated by SREBP1 and the FOXO3-SIRT6-Pcsk9 axis, while enhancing adipose triglyceride lipase activity via upregulation of Cgi-58 and downregulation of Elmod2. These molecular changes collectively reduce hepatic lipid accumulation, lower plasma LDL cholesterol, and alleviate alcohol-induced hepatic injury.

Figure 1. AAV8-mediated FAF2 knockdown reduced hepatic steatosis in ethanol-fed mice, as shown by H&E and Oil Red O staining, and decreased plasma AST, ALT, triglyceride, and cholesterol levels. (Huda N, et al., 2025)