NLRP3 inflammasome is involved in ambient PM_2.5-related metabolic disorders in diabetic model mice but not in wild-type mice

Abstract

Aims

To explore the role of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in ambient fine particulate matter (PM_2.5)-related metabolic disorders.

Methods

In this study, the C57BL/6 and db/db mice were exposed to concentrated PM_2.5 or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 12 weeks. Indices of lipid metabolism, glucose metabolism, insulin sensitivity, and protein expression of NLRP3 inflammasome in visceral adipose tissue (VAT) were measured, respectively.

Results

The results showed that PM_2.5 exposure increased circulatory insulin, triglycerides (TG), and total cholesterol (TC), and decreased high-density lipoprotein (HDL) in both C57BL/6 and db/db mice. The levels of NLRP3-related circulatory inflammatory cytokines including both interleukin (IL)-18 and IL-1β in serum were increased in the PM_2.5-exposed mice and accompanied by the elevation in fasting blood glucose and insulin. The results also showed that exposure to PM_2.5 promoted the activation of NLRP3, pro-caspase-1, caspase-1, and apoptosis-associated speck-like protein containing CARD (ASC), simultaneously accompanied by the increase of IL-18 and IL-1β expression in VAT, but the statistically significant difference only found in the db/db mice, not in C57BL/6 mice.

Conclusion

The activation of NLRP3 inflammasome might be not the main mechanism of PM_2.5-related metabolic disorders in wide type mice but it partly mediated the exacerbation of metabolic disorders in diabetic model mice.

Keywords:

• PM_2.5
• metabolic disorders
• insulin resistance
• inflammation
• NLRP3 inflammasome

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

Some or all data or models generated or used during the study are available from the corresponding author by request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [No. 81673125] and the National Key Research and Development Program of China [2016YFC0206600].