Endotoxins such as LPS intensify the damage of gut barrier proteins (such as ZO1) and induce TLR4 signaling 24, consequently promoting the production of pro-inflammatory cytokines (such as IL1β), which exacerbate systemic low-grade inflammation and accelerate obesity pathogenesis 26–28. Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.