TNF and obesity due to melanocortin 4 receptor deficiency: Regarding TLR-4, this receptor recognizes LPS as a ligand [41] and it was demonstrated that stimulation of adipocytes by LPS attenuates insulin signaling by stimulating NF-κB signaling, decreasing AKT phosphorylation, and increasing the expression of inflammatory cytokine genes such as TNF-α and IL-6 in 3T3-L1 adipocytes [42], which implicate this receptor in the onset of insulin resistance in obesity and type 2 diabetes.