Taken together, several proinflammatory cytokines, SOCS proteins, ER stress, the IKKβ pathway of NF-κB activation and JNK signaling pathways are all associated with the development of insulin resistance, indicating that various proinflammatory mediators released by adipocytes, in addition to the initially described proinflammatory cytokine TNF, link the immune system with obesity-related insulin resistance. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.