Accordingly, inhibition of hypothalamic IKKβ/NF-κB signaling effectively protects against these metabolic disorders, as shown by various experimental animal models including pharmacologic inhibition of hypothalamic IKKβ [35], brain-specific deletion of IKKβ [34], IKKβ/NF-κB signaling effector SOCS3 [45;231] or TLR4 signaling adaptor MyD88 [37], or whole-body genetic deficiency of NF-κB subunit p50 [232] or TLR4 [36;154]. This evidence concerns the gene NFKB1 and metabolic disease.