NLRP3 inflammasome is involved in ambient PM2.5-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 (PM2.5)-related metabolic disorders. Methods In this study, the C57BL/6 and db/db mice were exposed to concentrated PM2.5 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 PM2.5 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 PM2.5-exposed mice and accompanied by the elevation in fasting blood glucose and insulin. The results also showed that exposure to PM2.5 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 PM2.5-related metabolic disorders in wide type mice but it partly mediated the exacerbation of metabolic disorders in diabetic model mice.