Consistent with our previous finding that PIAS4 represses SIRT1 transcription in cancer cells [13, 14], we observed a decrease in SIRT1 levels in the livers of NASH mice compared to the control mice with concomitant increase in the binding of PIAS4 as well as HIC1-a known SIRT1 repressor and PIAS4 substrate-on the SIRT1 promoter region (Figure 1C). This evidence concerns the gene SIRT1 and metabolic dysfunction-associated steatohepatitis.