Beyond exacerbating steatosis and insulin resistance, hepatocyte NOX4 deficiency in HFD-fed C57BL/6 mice also facilitated the progression to NASH (Figure 7), with many of the key diagnostic features of human NASH (1), including hepatocyte ballooning (Figure 10, A and B), hepatocyte cell death, as reflected by TUNEL staining (Figure 10C), and lymphocytic infiltration, including CD3+ T cell infiltration, as assessed by histology (Figure 10D), immunohistochemistry (Figure 10E), and flow cytometry (Figure 10F and Supplemental Figure 10). This evidence concerns the gene NOX4 and metabolic dysfunction-associated steatohepatitis.