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Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR

During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, to...

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Autores principales: Küblbeck, Jenni, Niskanen, Jonna, Honkakoski, Paavo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602645/
https://www.ncbi.nlm.nih.gov/pubmed/33076503
http://dx.doi.org/10.3390/cells9102306
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author Küblbeck, Jenni
Niskanen, Jonna
Honkakoski, Paavo
author_facet Küblbeck, Jenni
Niskanen, Jonna
Honkakoski, Paavo
author_sort Küblbeck, Jenni
collection PubMed
description During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, together with other nuclear receptors (NRs) and transcription factors, in regulation of hepatic glucose and lipid metabolism, hepatocyte communication, proliferation and toxicity, and liver tumor development in rodents. Endocrine-disrupting chemicals (EDCs) constitute a wide range of persistent organic compounds that have been associated with aberrations of hormone-dependent physiological processes. Their adverse health effects include metabolic alterations such as diabetes, obesity, and fatty liver disease in animal models and humans exposed to EDCs. As numerous xenobiotics can activate CAR, its role in EDC-elicited adverse metabolic effects has gained much interest. Here, we review the key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein.
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spelling pubmed-76026452020-11-01 Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR Küblbeck, Jenni Niskanen, Jonna Honkakoski, Paavo Cells Review During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, together with other nuclear receptors (NRs) and transcription factors, in regulation of hepatic glucose and lipid metabolism, hepatocyte communication, proliferation and toxicity, and liver tumor development in rodents. Endocrine-disrupting chemicals (EDCs) constitute a wide range of persistent organic compounds that have been associated with aberrations of hormone-dependent physiological processes. Their adverse health effects include metabolic alterations such as diabetes, obesity, and fatty liver disease in animal models and humans exposed to EDCs. As numerous xenobiotics can activate CAR, its role in EDC-elicited adverse metabolic effects has gained much interest. Here, we review the key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein. MDPI 2020-10-15 /pmc/articles/PMC7602645/ /pubmed/33076503 http://dx.doi.org/10.3390/cells9102306 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Küblbeck, Jenni
Niskanen, Jonna
Honkakoski, Paavo
Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
title Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
title_full Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
title_fullStr Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
title_full_unstemmed Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
title_short Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
title_sort metabolism-disrupting chemicals and the constitutive androstane receptor car
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602645/
https://www.ncbi.nlm.nih.gov/pubmed/33076503
http://dx.doi.org/10.3390/cells9102306
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