TLR4 and obesity due to melanocortin 4 receptor deficiency: It is important to emphasize that the studies that investigated TLR4- and TLR5-deficient mice were performed without germ-free conditions [26],[27],[30], suggesting that the microbiota have an important influence on TLR5-deficient mice phenotype, inducing obesity and insulin resistance; however, in the TLR4-deficient mice, the microbiota do not have a role in these phenomena because these animals are protected from diet-induced insulin resistance, independently of germ-free conditions [26],[27].