This complex binds to toll-like receptor 4 (TLR4) on macrophages and adipose tissue, which activates the expression of genes encoding pro-inflammatory proteins, such as factor nuclear kappa B (NF-κB) and activator protein 1 (AP-1) [334,425], resulting in metabolic endotoxaemia (i.e., increased plasma LPS levels), which characterises both obesity and diabetes [415,426,427]. Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.