In obesity, along with peripheral and systemic inflammation, gut dysbiosis and LPS-mediated endotoxemia affect brain inflammation by enhancing the passage of circulating inflammatory cytokines across the blood–brain barrier (BBB) [52], stimulating microglia via TLR4 [53] and/or inhibiting vagal afferent neurons [54]. Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.