Activation of the signaling molecules such as Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), nuclear factor kappa B (NF-κB), inhibitor of nuclear factor kappa B kinase subunit beta (IKK), and c-Jun N-terminal kinase (JNK) is associated with the development of the obesity and the metabolic syndrome in the mediobasal hypothalamus [5,8,189]. The gene discussed is TLR4; the disease is obesity due to melanocortin 4 receptor deficiency.