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© 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
Author
Küblbeck, Jenni 1   VIAFID ORCID Logo  ; Niskanen, Jonna 2   VIAFID ORCID Logo  ; Honkakoski, Paavo 3   VIAFID ORCID Logo 

 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70210 Kuopio, Finland; [email protected]; School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70210 Kuopio, Finland; [email protected] 
 School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70210 Kuopio, Finland; [email protected] 
 School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70210 Kuopio, Finland; [email protected]; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus Box 7569, Chapel Hill, NC 27599-7569, USA 
First page
2306
Publication year
2020
Publication date
2020
Publisher
MDPI AG
e-ISSN
20734409
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2548338512
Copyright
© 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.