It is generally accepted that conditions associated with obesity such as increased fatty acids, microhypoxia, endoplasmic reticulum (ER) stress, and elevated cytokines activate pro-inflammatory responses in peripheral insulin target tissues by activating the c-Jun N-terminal kinase (JNK) and inhibiting the nuclear factor κB pathways, which in turn down-regulates insulin signaling (44). The gene discussed is MAPK8; the disease is obesity due to melanocortin 4 receptor deficiency.