NLRP3 inflammasome blocked the glycolytic pathway via targeting to PKLR in arsenic-induced hepatic insulin resistance

Ecotoxicology and Environmental Safety

卷:223

Xiance Sun¹  Liping Jiang²  Guang Yang³  Ningning Wang³  Xiaofang Liu³  Jie Bai³  Tianming Qiu⁴  Jingyuan Zhang⁴  Xiaofeng Yao⁴  Xiaoxia Shi⁴  Yuhan Zhu⁴  Shengyu Wang⁵  Rushan Yan⁶ 

[1] Correspondence to: Department of Occupational and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China.;

[2] Experimental Teaching Center of Public Health, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China;

[3] Nutrition and Food Hygiene, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China;

[4] Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China;

[5] The First Affiliated Hospital, Dalian Medical University, 222 Zhongshan Road, Dalian 116001, PR China;

[6] The Second Affiliated Hospital, Dalian Medical University, 467 Zhongshan Road, Dalian 116023, PR China;

关键词: NaAsO2;    NLRP3 inflammasome;    Glycolysis;    Hepatic insulin resistance;   

DOI  :  

来源: DOAJ

【 摘 要 】

Arsenic exposure is related to insulin resistance (IR). However, the underlying mechanism is still uncertain. NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a key driving factor of IR. We found that NaAsO2 caused hepatic IR, activated NLRP3 inflammasome, and inhibited glycolysis pathway in vivo. We also found that tricarboxylic acid cycle (TCA cycle) was inhibited, and the content of hepatic lactate was upregulated with the treatment of arsenic. Consistent with these findings, we found that NLRP3 inflammasome and glycolysis were involved in the development of IR in L-02 cells. Besides, inhibiting NLRP3 inflammasome upregulated aerobic glycolysis and inhibited anaerobic glycolysis. Moreover, we demonstrated that NLRP3 inflammasome could bind to pyruvate kinase, liver and RBC (PKLR). Simultaneously, insulin signaling rather than NLRP3 inflammasome activation was altered by overexpressing PKLR. In summary, after treatment with NaAsO2, NLRP3 inflammasome blocked the glycolytic pathway via binding to PKLR, which in turn caused hepatic IR. This study shed new light on the molecular mechanism underlying arsenic-induced IR.

【 授权许可】

Unknown