Obesity has been associated with activation of pro-inflammatory pathways in the brain, as a high fat diet up-regulated expression of toll like receptor 4 (TLR4), high-mobility group protein B1 (HMGB1), vascular endothelial growth factor (VEGF) and COX-2 [155]. Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.