We and others have shown that experimental endotoxemia induces adipose inflammation, insulin resistance, and HDL dysfunction in humans.14–18 Furthermore, endogenous ligands generated in obesity and atherosclerosis, such as fatty acids and modified lipids, can promote Toll-like receptor-4 signaling.34 In fact, deletion of Toll-like receptor-4 attenuated diet-induced obesity, insulin resistance,35 and atherosclerosis36 in rodent models. This evidence concerns the gene TLR4 and obesity due to melanocortin 4 receptor deficiency.