Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-?B signalling via downregulation of HNF1b

Polychlorinated biphenyls (PCB) is a major type of persistent organic pollutants (POPs) that act as endocrine-disrupting chemicals. In the current study, the authors examined the mechanism underlying the effect of PCB-153 on glucose and lipid metabolism in vivo and in vitro. It was 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-?B and the expression of its downstream inflammatory markers, and worsened HFD-resulted increase of those inflammatory markers. Inhibition of NF-?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-?B-mediated inflammation, and final glucose/lipid metabolic disorder. The authors concluded that the results suggest that dysregulation of HNF1b/ROS/NF-?B plays an important role in PCB-153-induced glucose/lipid metabolic disorder.

Authors: Wu H, Yu W, Meng F, Mi J, Peng J, Liu J, Zhang X, Hai C, Wang X. ;Full Source: Redox Biology. 2017 Mar 7; 12:300-310. doi: 10.1016/j.redox.2017.02.026. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Epub ahead of print] ;[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]