Under metabolic stress, hepatic activation occurs through dual pathways: 1) hepatocyte FFA accumulation triggers oxidative/ER stress, stimulating Kupffer cells to release pro-inflammatory cytokines (IL-6, TNF-α) that amplify systemic inflammation via portal circulation; 2) steatotic hepatocytes secrete aberrant adipokines (reduced adiponectin, elevated resistin) synergizing with visceral fat-derived adipokines to promote atherosclerosis (39, 40). The gene discussed is RETN; the disease is atherosclerosis.