Injection of lentivirus carrying interfering RNA against PIAS4 (shPias4) into the NASH mice induced by the HFHC diet resulted in ~80% decrease in PIAS4 expression in the liver compared to the NASH mice injected with an empty vector (SCR) as measured by qPCR (Figure 3A); PIAS4 silencing led to a significant up-regulation of SIRT1 expression in the liver (Figure 3A). Here, PIAS4 is linked to metabolic dysfunction-associated steatohepatitis.