In the present report, using hepatocyte-specific Trim31 deficiency (THKO)/transgenic mice (THTG) and lentivirus-mediated ex vivo gene therapy (LV-Trim31) mice, we identified liver Trim31 as a significant protective regulator against HFD/HFHF-stimulated or genetically induced inflammation, insulin resistance, liver steatosis, and NASH. Here, TRIM31 is linked to Insulin resistance.