While under normal conditions, the gut barrier only allows a minimal amount of LPS to enter the circulation, the elevated LPS in obesity and DM binds to TLR4 and activates NF-κB signaling pathways, promoting the secretion of inflammatory cytokines like IL-1, IL-6, and TNF-α (132, 133). The gene discussed is NFKB1; the disease is obesity due to melanocortin 4 receptor deficiency.