TLR4 and obesity due to melanocortin 4 receptor deficiency: While it is likely that central inflammation in obesity results from adiposity-related systemic inflammatory processes, the increases in circulating levels of TLR4 ligands and free saturated fatty acids following impaired gut permeability in high-fat diet mice (68, 80) may alternatively contribute to central inflammation, through activation of TLR4/MyD88 signaling (81, 82).