Intestinal permeability is a key determinant of NAFLD development, gut-derived LPS through the portal vein arrive in the liver drain bind to its natural ligand TLR4 and activates the downstream nuclear factor kappa-B (NF-κB) through the myeloid differentiation factor 88 (MyD88)-dependent signaling pathway, inducing the expression of TNF-α, IL-1, IL-6 and other inflammatory cytokines, and promoting M1 macrophages activation (Kazankov et al., 2019). The gene discussed is TLR4; the disease is metabolic dysfunction-associated steatotic liver disease.