Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b

Redox Biol. 2017 Aug;12:300-310. doi: 10.1016/j.redox.2017.02.026. Epub 2017 Mar 7.

Abstract

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 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-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.

Keywords: Glucose and lipid metabolic disorder; Hepatocyte nuclear factor 1b; NF-κB; Polychlorinated biphenyls; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Cell Line
  • Diet, High-Fat / adverse effects
  • Down-Regulation*
  • Glucose Intolerance / chemically induced
  • Hepatocyte Nuclear Factor 1-beta / metabolism*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Lipid Metabolism / drug effects
  • Male
  • Metabolic Syndrome / chemically induced*
  • Metabolic Syndrome / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Polychlorinated Biphenyls / adverse effects*
  • Polychlorinated Biphenyls / pharmacology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*

Substances

  • Hnf1b protein, mouse
  • NF-kappa B
  • Reactive Oxygen Species
  • Hepatocyte Nuclear Factor 1-beta
  • Polychlorinated Biphenyls
  • 2,4,5,2',4',5'-hexachlorobiphenyl