Altogether, our results show for the first time a direct lipotoxic effect of n/oxLDL on renal tubular cells and validate NLRP3 involvement in the onset and progression of metabolic disorders and suggest the potential of specifically targeting NLRP3 as a therapeutic approach to counteract or attenuate obesity/MetS-driven renal pathology. The gene discussed is NLRP3; the disease is metabolic disease.