Increases of ROS, FFA, and TNF-α during chronic inflammation and obesity triggers activation of JNK in hepatocytes and macrophages, thus increasing production of inflammatory cytokines that drives inflammation, apoptosis, liver injury and fibrosis, and hepatic IR, thereby highlighting the metabolic effects of the JNK pathway (114). Here, MAPK8 is linked to obesity due to melanocortin 4 receptor deficiency.