In obesity and hyperinsulinemia, the increased FFAs, ROS and TNF-α lead to JNK activation in hepatocytes and macrophages, which can increase the production of inflammatory cytokines that can cause inflammation, apoptosis, hepatic IR, liver injury and fibrosis, supporting the metabolic contribution of JNK pathway (66, 170). The gene discussed is MAPK8; the disease is obesity due to melanocortin 4 receptor deficiency.