Activation of these kinases in obesity highlights the intertwined relationship of metabolic and immune pathways; JNK and IKK are the same kinases that are activated in the innate immune response, mediated by Toll-like receptor (TLR) signaling stimulated by lipopolysaccharide (LPS), peptidoglycan, double-stranded RNA, and other microbial products (Figure 2). This evidence concerns the gene MAPK8 and obesity due to melanocortin 4 receptor deficiency.