CLDN5 and obesity due to melanocortin 4 receptor deficiency: HFD-fed rats specifically show changes to their tight junction proteins such as claudin-5 and claudin-12 with other mouse models showing obesity-induced downregulation of cytoskeletal proteins: vimentin and tubulin; both of which are involved in nutrient transport.36 Increased oxidative stress due to obesity contributes to perturbed BBB functioning.