Background:Heatwave events occur more frequently,accompanied by a significant increase in the ambient concentration of fine particulate matter(PM 2.5).Epidemiological and experimental studies have suggested that heat ...Background:Heatwave events occur more frequently,accompanied by a significant increase in the ambient concentration of fine particulate matter(PM 2.5).Epidemiological and experimental studies have suggested that heat stress or PM 2.5 exposure would impair glucose homeostasis and insulin sensitivity.Objective:To explore the joint effects of heat stress and PM 2.5 exposure on glucose metabolism and hepatic insulin pathway.Methods:C57BL/6 mice were randomly divided into filtered air(FA)group,fine particulate matter(PM)group,filtered air combined with heat stress(FH)group,and PM combined with heat stress(PH)group.Mice were exposed to PM for a total of 6 weeks,and heat stress combined with PM exposure was applied at the 5th and 6th weeks 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 less-ened hepatic GLUT2 expression and inhibited insulin signaling pathway.No synergistic effects of heat stress and PM 2.5 exposure on glucose homeostasis were observed,while heat-upregulated HSP72 expression was attenuated with accumulated TNF𝛼induced by further PM 2.5 exposure.Conclusion:Heat stress combined with PM 2.5 exposure induced TNF𝛼,which could inhibit heat-elevated hepatic HSP72 expression.Elevated circulating TNF𝛼impaired hepatic insulin signaling and GLUT2 expression.Then,glucose homeostasis was perturbed,and insulin action was impaired.展开更多
基金supported by Key R&D International Cooperation Projects(Grant No:2019YFE0114500)National Natural Science Foun-dation of China(Grant Nos:81904027,81973001)+1 种基金Medical Health Sci-ence and Technology Project of Zhejiang Provincial Health Commis-sion(Grant Nos:2018KY545,2019KY471,2019KY472)Natural Science Foundation of Zhejiang Chinese Medical University(Grant Nos:2014ZR03,KC201901,2019ZR02,2019ZZ04).
文摘Background:Heatwave events occur more frequently,accompanied by a significant increase in the ambient concentration of fine particulate matter(PM 2.5).Epidemiological and experimental studies have suggested that heat stress or PM 2.5 exposure would impair glucose homeostasis and insulin sensitivity.Objective:To explore the joint effects of heat stress and PM 2.5 exposure on glucose metabolism and hepatic insulin pathway.Methods:C57BL/6 mice were randomly divided into filtered air(FA)group,fine particulate matter(PM)group,filtered air combined with heat stress(FH)group,and PM combined with heat stress(PH)group.Mice were exposed to PM for a total of 6 weeks,and heat stress combined with PM exposure was applied at the 5th and 6th weeks 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 less-ened hepatic GLUT2 expression and inhibited insulin signaling pathway.No synergistic effects of heat stress and PM 2.5 exposure on glucose homeostasis were observed,while heat-upregulated HSP72 expression was attenuated with accumulated TNF𝛼induced by further PM 2.5 exposure.Conclusion:Heat stress combined with PM 2.5 exposure induced TNF𝛼,which could inhibit heat-elevated hepatic HSP72 expression.Elevated circulating TNF𝛼impaired hepatic insulin signaling and GLUT2 expression.Then,glucose homeostasis was perturbed,and insulin action was impaired.