MAPK8 and obesity due to melanocortin 4 receptor deficiency: Previous studies have demonstrated that TLR4 may be a central link between insulin resistance, inflammation and obesity, and that a point mutation in TLR4, which inactivates the receptor, prevents the diet-induced obesity (DIO) activation of IκB kinase (IKKβ) and c-Jun NH2-terminal kinase (JNK), and inhibits insulin resistance, suggesting that TLR4 is a key modulator in the cross-talk between inflammatory and metabolic pathways (3–8).