In contrast, brain knockout or central pharmacological inhibition of TLR4 or IKKβ/NF-κB prevents hypothalamic inflammation, improves leptin sensitivity and protects against HFD-induced obesity (Zhang et al., 2008; Kleinridders et al., 2009; Milanski et al., 2009; Meng and Cai, 2011). The gene discussed is IKBKB; the disease is obesity due to melanocortin 4 receptor deficiency.