The studies, together with the subsequent identification of two key molecules downstream of the transmembrane cytokine receptors, namely the inhibitor of kappa B kinase (IKKb), an important element of NF-κB pathway, and c-Jun NH2-terminal kinase (JNK), were critical in our understanding of the link between the processes involved in nutrient overload, obesity and impaired insulin action with immune-related intracellular signal transduction pathways [45,55,59,60]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.