In summary, the combination of HFD and DMN-induced steatohepatitis and fibrosis with the enhancement of inflammatory cytokines and activation of NF-κB and JNK signaling in the liver of Cx32ΔTg rats; as well as hepatic histological changes, obesity, and IR were observed. This evidence concerns the gene MAPK8 and obesity due to melanocortin 4 receptor deficiency.