Bacterial lipopolysaccharide9,11 and peptidoglycan32 represent two classic examples accounting for obesity-related insulin resistance during metabolic endotoxemia, by activating Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-containing (NOD) proteins (NOD133–35 and NOD236,37), respectively. The gene discussed is TLR4; the disease is obesity due to melanocortin 4 receptor deficiency.