TLR4 and obesity due to melanocortin 4 receptor deficiency: Studies in mice demonstrated that a HF diet or LPS infusion induced a two- to threefold increase in circulating LPS levels, contributing to the development of obesity and increased insulin resistance [32,33], and vice versa, LPS and TLR4 initiate a well-characterized signaling cascade that elicits intricate pro-oxidant and pro-inflammatory pathways in obesity [34].