ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Polychlorinated Biphenyl-Xenobiotic Nuclear Receptor Interactions Regulate Energy Metabolism, Behavior, and Inflammation in Non-alcoholic-Steatohepatitis.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 65 citations in OpenAlex.
- 3,3'-Dichlorobiphenyl (PCB 11) alters the hepatic expression of cytochrome P450 enzymes in the liver of mouse dams exposed orally during pregnancy and lactation.Archives of toxicology · 2026Article
- Article
- Sex-dependent modulation of PCB-mediated toxicity from a proteomic and microbiome perspective.Scientific reports · 2025Article
- Targeting nuclear receptors for NASH/MASH: From bench to bedside.Liver research (Beijing, China) · 2024Article
- Sex-specific effects of acute chlordane exposure in the context of steatotic liver disease, energy metabolism and endocrine disruption.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- Altered splicing factor and alternative splicing events in a mouse model of diet- and polychlorinated biphenyl-induced liver disease.Environmental toxicology and pharmacology · 2023Article
- Exposure to polychlorinated biphenyls selectively dysregulates endothelial circadian clock and endothelial toxicity.Journal of hazardous materials · 2023Article
- Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- Disruption of the mouse liver epitranscriptome by long-term aroclor 1260 exposure.Environmental toxicology and pharmacology · 2023Article
- Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease.Frontiers in public health · 2023Review
- Investigating the effects of long-term Aroclor 1260 exposure on fatty liver disease in a diet-induced obesity mouse model.Frontiers in gastroenterology (Lausanne, Switzerland) · 2023Article
- Recombinant FGF21 Attenuates Polychlorinated Biphenyl-Induced NAFLD/NASH by Modulating Hepatic Lipocalin-2 Expression.International journal of molecular sciences · 2022Article
- Pregnane X receptor exacerbates nonalcoholic fatty liver disease accompanied by obesity- and inflammation-prone gut microbiome signature.Biochemical pharmacology · 2021Article
- Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis.Environmental health perspectives · 2021Article
- Polychlorinated biphenyls altered gut microbiome in CAR and PXR knockout mice exhibiting toxicant-associated steatohepatitis.Toxicology reports · 2021Article
- Review
- Review
- Dioxin-like and non-dioxin-like PCBs differentially regulate the hepatic proteome and modify diet-induced nonalcoholic fatty liver disease severity.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
- Insecticide and metal exposures are associated with a surrogate biomarker for non-alcoholic fatty liver disease in the National Health and Nutrition Examination Survey 2003-2004.Environmental science and pollution research international · 2020Article
- Understanding the Multiple Effects of PCBs on Lipid Metabolism.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis and activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate PCB interactions with the pregnane-xenobiotic receptor (Pxr: Nr1i2) and constitutive androstane receptor (Car: Nr1i3) in NASH. Wild type C57Bl/6 (WT), Pxr(-/-) and Car(-/-) mice were fed the high fat diet (42% milk fat) and exposed to a single dose of Aroclor 1260 (20 mg/kg) in this 12-week study. Metabolic phenotyping and analysis of serum, liver, and adipose was performed. Steatohepatitis was pathologically similar in all Aroclor-exposed groups, while Pxr(-/-) mice displayed higher basal pro-inflammatory cytokine levels. Pxr repressed Car expression as evident by increased basal Car/Cyp2b10 expression in Pxr(-/-) mice. Both Pxr(-/-) and Car(-/-) mice showed decreased basal respiratory exchange rate (RER) consistent with preferential lipid metabolism. Aroclor increased RER and carbohydrate metabolism, associated with increased light cycle activity in both knockouts, and decreased food consumption in the Car(-/-) mice. Aroclor exposure improved insulin sensitivity in WT mice but not glucose tolerance. The Aroclor-exposed, Pxr(-/-) mice displayed increased gluconeogenic gene expression. Lipid-oxidative gene expression was higher in WT and Pxr(-/-) mice although RER was not changed, suggesting PCB-mediated mitochondrial dysfunction. Therefore, Pxr and Car regulated inflammation, behavior, and energy metabolism in PCB-mediated NASH. Future studies should address the 'off-target' effects of PCBs in steatohepatitis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.