TLR4 and obesity due to melanocortin 4 receptor deficiency: In a mouse model of obesity, hyperleptinemia associated with obesity is reported to activate STAT3 signaling in Kupffer cells, which in turn increases the expression of CD14, a co-receptor of TLR4, and induces an excessive inflammatory response of the liver to endotoxin, leading to the development of NASH pathology [32].