INS and obesity due to melanocortin 4 receptor deficiency: However, in obesity there is an increase in production and release of pro-inflammatory cytokines, from the fat tissue infiltrated with macrophages, along with increase of free fatty acids from lipolysis and intake of saturated fat-rich diet that cause damages to insulin signaling and hyperglycemia.(22) Recent studies had observed that some types of fatty acids from diet, especially the saturated fatty acids, are capable to linking and activating proteins of membrane named TollLikeReceptor 4 (TLR4).