Given the significant correlation between NAFLD and renal fibrosis, we propose the central hypothesis that ANGPTL8 derived from NAFLD activates the ALOX5AP pathway in renal CCR2+PIRB+ macrophages via PIRB, reprogramming linoleic acid metabolism, and driving profibrotic inflammation. The gene discussed is CCR2; the disease is metabolic dysfunction-associated steatotic liver disease.