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Tags
HERO ID
3872275
Reference Type
Journal Article
Title
Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b
Author(s)
Wu, H; Yu, W; Meng, F; Mi, J; Peng, J; Liu, J; Zhang, X; Hai, C; Wang, X
Year
2017
Is Peer Reviewed?
1
Journal
Redox Biology
ISSN:
2213-2317
Volume
12
Issue
August 2017
Page Numbers
300-310
Language
English
PMID
28285191
DOI
10.1016/j.redox.2017.02.026
Web of Science Id
WOS:000403328700029
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
Polychlorinated biphenyls; Glucose and lipid metabolic disorder; Hepatocyte nuclear factor 1b; Reactive oxygen species; NF-κB
Tags
IRIS
•
PCBs
Mechanistic
Supplemental
Litsearches
LitSearch: August 2016-August 2017
PubMed
Toxline
WoS
•
PCBs Tox Hazard ID
Administered mixture of < 4 individual PCB congeners
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