2. Academic Validation
  3. NLRP3 inflammasome blocked the glycolytic pathway via targeting to PKLR in arsenic-induced hepatic insulin resistance

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

  • Ecotoxicol Environ Saf. 2021 Oct 15;223:112590. doi: 10.1016/j.ecoenv.2021.112590.
Jingyuan Zhang 1,  Tianming Qiu 2,  Liping Jiang 3,  Ningning Wang 4,  Yuhan Zhu 5,  Rushan Yan 6,  Shengyu Wang 7,  Jie Bai 8,  Xiaoxia Shi 9,  Guang Yang 10,  Xiaofang Liu 11,  Xiaofeng Yao 12,  Xiance Sun 13
Affiliations

Affiliations

  • 1 Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 2 Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 3 Experimental Teaching Center of Public Health, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 4 Nutrition and Food Hygiene, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 5 Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 6 The Second Affiliated Hospital, Dalian Medical University, 467 Zhongshan Road, Dalian 116023, PR China. Electronic address: [email protected].
  • 7 The First Affiliated Hospital, Dalian Medical University, 222 Zhongshan Road, Dalian 116001, PR China. Electronic address: [email protected].
  • 8 Nutrition and Food Hygiene, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 9 Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 10 Nutrition and Food Hygiene, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 11 Nutrition and Food Hygiene, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 12 Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 13 Occupational and Environmental Health Department, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China; Global Health Research Center, Dalian Medical University, 9 Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
PMID: 34364127 DOI: 10.1016/j.ecoenv.2021.112590
Abstract

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.

Keywords

Glycolysis; Hepatic insulin resistance; NLRP3 inflammasome; NaAsO(2).

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