Additionally, studies on mice have shown that the activation of c-Jun N-terminal kinase 1 (JNK1) and inhibitor of nuclear factor kappa-B kinase 2 (IKK2) plays a key role in the development of insulin and leptin resistance in AgRP neurons and, therefore, increased appetite and obesity development [48]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.