Through activity on multiple oncogenic molecular pathways (e.g. inhibitor of kappa kinase IKK/c-Jun amino-terminal kinases JNK, signal transducer and activator of transcription STAT and NF-κB pathways), high levels of cytokines trigger IR, oxidative stress, lipotoxicity, hepatocyte cell death, liver inflammation, fibrosis, and pathological angiogenesis, thus promoting the progression from simple obesity-related hepatic steatosis to HCC (26, 80, 93). Here, MAPK8 is linked to obesity due to melanocortin 4 receptor deficiency.