Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signalin

• 作 者: Zi Long Xin Wan Chunxu Hai
• 机 构: Department of Toxicology,Shaanxi Key Lab of Free Radical Biology and Medicine,School of Public Healt
• 出 处: 中国环境诱变剂学会第七届全国会员代表大会暨第十七次学术大会
• 发表日期: 2017年3期
• 关键词: polychlorinated biphenyls glucose and lipid metabolic disorder hepatocyte nuclea

　　Polychlorinated biphenyls(PCB)is a major type of persistent organic pollutants(POPs)that act as endocrine-disrupting chemicals.In the current study,we examined the mechanism underlying the effect of PCB-153 on glucose and lipid metabolism in vivo and in vitro.We found that PCB-153 induced per se and worsened high fat diet(HFD)-resulted increase of blood glucose level and glucose and insulin intolerance.In addition,PCB-153 induced per se and worsened HFD-resulted increase of triglyceride content and adipose mass.Moreover,PCB-153 concentration-dependently inhibited insulin-dependent glucose uptake and lipid accumulation in cultured hepatocytes and adipocytes.PCB-153 induced the expression and nuclear translocation of p65 NF-κB and the expression of its downstream inflammatory markers,and worsened HFD-resulted increase of those inflammatory markers.Inhibition of NF-κB significantly suppressed PCB-153-induced inflammation,lipid accumulation and decrease of glucose uptake.PCB-153 induced oxidative stress and decreased hepatocyte nuclear factor lb(HNFlb)and glutathione peroxidase 1(GPx1)expression in vivo and in vitro.Overexpression of HNFlb increased GPxl expression,decreased ROS level,decreased Srebpl,ACC and FAS expression,and inhibited PCB-153-resulted oxidative stress,NF-κB-mediated inflammation,and final glucose/lipid metabolic disorder.Our results suggest that dysregulation of HNF1b/ROS/NF-κB plays an important role in PCB-153-induced glucose/lipid metabolic disorder.