INSR and obesity due to melanocortin 4 receptor deficiency: Moreover, FFA can bind to Toll-like receptors 4 (TLR-4) in immune cells during obesity and activate the canonical nuclear factor kappa B (NF-κB) pathway, promoting the synthesis of proinflammatory cytokines that activate c-Jun N-terminal kinase (JNK) and suppressor of cytokine signaling (SOCS) impeding the binding of IRS 1/2 to the insulin receptor and disrupting insulin signaling [56,57].