Joint Effects of Heat Stress and PM2.5 Exposure on Glucose Metabolism and Hepatic Insulin Signaling

Background: Heatwave events are occurring more frequently, accompanied by a significant increase in the ambient concentration of fine particulate matter (PM2.5). Epidemiological studies have suggested that heat stress or PM2.5 exposure would impair glucose homeostasis and insulin sensitivity, but the combined effect and the exact mechanisms are not well understood.Methods: C57BL/6 mice were randomly divided into filtered air (FA), fine particulate matter (PM) group, filtered air combined with heat stress (FH) group, and fine particulate matter combined with heat stress (PH) group for a 4-week PM2.5 exposure, followed by a 2-week heat stress exposure, via a whole-body exposure system. Systemic glucose homeostasis, insulin sensitivity, and circulating inflammatory cytokines were examined. HSP72 expression and insulin signaling in the liver were measured.Results: Glucose tolerance and insulin sensitivity were impaired in response to heat stress, accompanied by lessened hepatic GLUT2 expression and inhibited insulin signaling pathway. No synergistic effects of heat stress and PM2.5 exposure on glucose homeostasis were observed, while heat-upregulated HSP72 expression was attenuated with accumulated TNF-α induced by further PM2.5 exposure.Conclusions: Heat stress combined with PM2.5 exposure induced TNF-α, which could inhibit heat-elevated hepatic HSP72 expression. Elevated circulating TNF-α impaired hepatic insulin signaling and GLUT2 expression. Then, glucose homeostasis was perturbed, and insulin action was impaired.