In conclusion, the present study identified a novel effect of hepatocyte TRAF3 on hepatic steatosis that is dependent on the interaction of TRAF3 with TAK1, which promotes the ubiquitination and phosphorylation of TAK1 and enhances the activation of downstream JNK and NF-κB cascades, thereby promoting insulin resistance, gluconeogenesis, inflammatory response and lipid accumulation in the liver on an HFD stimulus. This evidence concerns the gene MAPK8 and fatty liver disease.