The activation of TLR4 signaling induces upregulation of inflammatory pathways related to the induction of insulin resistance, such as c-Jun NH2-terminal kinase (JNK) and IκB kinase complex (IKKβ)/inhibitor of nuclear factor-κB (IκBα)/nuclear factor-κB (NF-κB) [87,95], while loss-of-function mutation and knockout in TLR4 prevents insulin resistance induced by obesity or free fatty acids, suggesting an important role of TLR4 in the interface of innate immune system and energetic metabolism [95,96,97,98,99,100,101,102] (Figure 2). This evidence concerns the gene TLR4 and obesity disorder.