Journal
REDOX BIOLOGY
Volume 12, Issue -, Pages 300-310Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2017.02.026
Keywords
Polychlorinated biphenyls; Glucose and lipid metabolic disorder; Hepatocyte nuclear factor 1b; Reactive oxygen species; NF-kappa B
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Funding
- National Natural Science Foundation of China [31400724, 21677176]
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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-kappa B and the expression of its downstream inflammatory markers, and worsened HFD-resulted increase of those inflammatory markers. Inhibition of NF-kappa B significantly suppressed PCB-153-induced inflammation, lipid accumulation and decrease of glucose uptake. PCB-153 induced oxidative stress and decreased hepatocyte nuclear factor 1b (HNF1b) and glutathione peroxidase 1 (GPx1) expression in vivo and in vitro. Overexpression of HNF1b increased GPx1 expression, decreased ROS level, decreased Srebp1, ACC and FAS expression, and inhibited PCB-153-resulted oxidative stress, NF-kappa B-mediated inflammation, and final glucose/lipid metabolic disorder. Our results suggest that dysregulation of HNF1b/ROS/NF-kappa B plays an important role in PCB-153-induced glucose/lipid metabolic disorder.
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