TLR4 and obesity due to melanocortin 4 receptor deficiency: For example, Wu et al. [28] demonstrated that chronic aerobic exercise reduced TLR4, and other articles have demonstrated that the beneficial effects of TLR4 downregulation mediated by physical exercise could act in a variety of chronic conditions other than cardiovascular disease such as insulin resistance in people with type 2 diabetes mellitus and obesity, and inflammation [28].