ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.
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 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Gut microbiota restricts intestinal lipid uptake via modulation of bile phosphatidylcholine metabolism in mice.Nature microbiology · 2026Article
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Bile acids and their receptors in hepatic immunity.Liver research (Beijing, China) · 2025Review
- Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review.Biomedicines · 2024Review
- The xenobiotic receptors PXR and CAR in liver physiology, an update.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Bile Acids as a New Type of Steroid Hormones Regulating Nonspecific Energy Expenditure of the Body (Review).Sovremennye tekhnologii v meditsine · 2021Review
- Perfluorooctanoic acid activates multiple nuclear receptor pathways and skews expression of genes regulating cholesterol homeostasis in liver of humanized PPARα mice fed an American diet.Toxicology and applied pharmacology · 2020Article
- Effects of ablation and activation of Nrf2 on bile acid homeostasis in male mice.Toxicology and applied pharmacology · 2020Article
- Effects of patent ductus venosus on bile acid homeostasis in aryl hydrocarbon receptor (AhR)-null mice.Toxicology and applied pharmacology · 2020Article
- Constitutive androstane receptor mediates PCB-induced disruption of retinoid homeostasis.Toxicology and applied pharmacology · 2019Article
- Pharmacological Activation of PXR and CAR Downregulates Distinct Bile Acid-Metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Constitutive Androstane Receptor Differentially Regulates Bile Acid Homeostasis in Mouse Models of Intrahepatic Cholestasis.Hepatology communications · 2019Article
- PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Aryl hydrocarbon receptor (AhR) mediated short-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid homeostasis in mice.Toxicology and applied pharmacology · 2018Article
- Editor's Highlight: Neonatal Activation of the Xenobiotic-Sensors PXR and CAR Results in Acute and Persistent Down-regulation of PPARα-Signaling in Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver.
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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.