2. Academic Validation
  3. Annexin A1 inhibition facilitates NLRP3 inflammasome activation in arsenic-induced insulin resistance in rat liver

Annexin A1 inhibition facilitates NLRP3 inflammasome activation in arsenic-induced insulin resistance in rat liver

  • Environ Toxicol Pharmacol. 2022 Sep 28;96:103981. doi: 10.1016/j.etap.2022.103981.
Chenbing Wu 1,  Tianming Qiu 2,  Weizhuo Yuan 3,  Yan Shi 4,  Xiaofeng Yao 5,  Liping Jiang 6,  Jingyuan Zhang 7,  Guang Yang 8,  Xiaofang Liu 9,  Jie Bai 10,  Danyi Zhao 11,  Xiance Sun 12
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 2 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 3 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 4 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 5 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 6 Preventive Medicine Laboratory, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, 116044, PR China. Electronic address: [email protected].
  • 7 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 8 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 9 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 10 Department of Nutrition and Food Safety, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
  • 11 Department of Gastrointestinal Oncology, The Second Hospital of Dalian Medical University, Dalian, PR China. Electronic address: [email protected].
  • 12 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address: [email protected].
PMID: 36182042 DOI: 10.1016/j.etap.2022.103981
Abstract

Hepatic Insulin resistance (IR) is the primary pathology of type 2 diabetes (T2D). The role of the NOD-like receptor protein 3 (NLRP3) inflammasome in arsenic-induced hepatic IR has been previously demonstrated. However, the mechanism of the arsenic-induced activation of the NLRP3 inflammasome is still unclear. Here, we demonstrate that NaAsO2 downregulated the mRNA and protein level of Annexin A1 (AnxA1), an anti-inflammatory factor, in rat livers and L-02 cells. Moreover, AnxA1 overexpression significantly alleviated arsenic-induced NLRP3 inflammasome activation and IR in L-02 cells. Importantly, Co-immunoprecipitation (Co-IP) results showed that AnxA1 1-190 peptide could bind to the domain encompassing Amino acids 1-210 and 211-550 of NLRP3. In conclusion, our experiments demonstrated that arsenic exposure could activate the NLRP3 inflammasome and IR by inhibiting the AnxA1 activity. These findings suggest that AnxA1 may be a promising therapeutic target of arsenicosis.

Keywords

Annexin A1; Arsenic; Insulin resistance; NLRP3; Type 2 diabetes.

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