Cytokines, ROS, endoplasmic reticulum stress, and free fatty acids activate JNK (Ozcan et al., 2004; Holzer et al., 2011; Zhao H. et al., 2015) and play a key role in metabolic disorders such as obesity, IR, and T2D (Vallerie and Hotamisligil, 2010). The gene discussed is MAPK8; the disease is obesity due to melanocortin 4 receptor deficiency.