We found that compared with HFHC-challenged FAKflox/LV-shDUSP22 mice, the phenotypes indicating NASH progression including liver weight, the ratio of LW/BW, blood glucose levels, fasting insulin contents, HOMA-IR index, and serum concentrations of ALT and AST were considerably mitigated in LV-shDUSP22 mice with FAKHepKO although no significant difference was detected in the body weight changes (Supplementary Fig. 22c–i). Here, INS is linked to metabolic dysfunction-associated steatohepatitis.