#3581 ACSS2-INDUCED FATTY ACID SYNTHESIS PROMOTES NLRP3 INFLAMMASOME AND PYROPTOSIS OF RENAL TUBULAR CELLS IN SEPSIS-INDUCED ACUTE KIDNEY INJURY

Abstract Background and Aims Cellular fatty acid metabolism was supposed to be tightly associated with immune responses. Pyroptosis is a form of programmed cell death dependent on the NLRP3 inflammasome activation. Previous studies have revealed that acyl-CoA synthetase 2 (ACSS2) promoted synthesis under metabolic stress. However, whether ACSS2-mediated can regulate pyroptosis inflammatory responses renal tubular cells in AKI remain unclear. Method lipopolysaccharide (LPS) intraperitoneally injected establish sepsis mouse model, vitro HK-2 culture model achieved by LPS stimulation. HE PAS staining were carried out evaluate pathological injury kidneys mice. The tissue immunostaining conducted detect IL-1β expression macrophage distribution kidney tissues Gene factors evaluated real-time PCR. Western Blot activation pathway vivo vitro. Results Here, we demonstrated ACSS2 significantly increased epithelial mice Lipopolysaccharide (LPS)-induced when compared wild-type regulates NLRP3-mediated caspase-1 production through stimulation synthase (FASN) cells. deletion attenuated infiltration an LPS-induced model. Consistently, ACSS2-deficient displayed impaired FASN-mediated lipid decreased response challenge. In cells, deficiency suppressed downregulation FASN. treatment chemical inhibitor C75 Conclusion Our results suggested regulated inducing These identified as potential therapeutic target AKI.