ArticleBMC genomics2009
Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers.
Article in BMC genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Environmental Endocrine-Disrupting Chemicals and Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Pooled it
- Perfluorooctanoic acid increases serum cholesterol in a PPARα-dependent manner in female mice.Archives of toxicology · 2025Article
- The hypolipidemic effect of MI-883, the combined CAR agonist/ PXR antagonist, in diet-induced hypercholesterolemia model.Nature communications · 2025Article
- Review
- Discovery of Novel Human Constitutive Androstane Receptor Agonists with the Imidazo[1,2-Journal of medicinal chemistry · 2023Article
- Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice.International journal of molecular sciences · 2023Article
- Perfluorooctanoic acid induces liver and serum dyslipidemia in humanized PPARα mice fed an American diet.Toxicology and applied pharmacology · 2021Article
- De novo assembly of the transcriptome of scleractinian coral, Anomastraea irregularis and analyses of its response to thermal stress.Molecular biology reports · 2021Article
- Quantifying simultaneous innovations in evolutionary medicine.Theory in biosciences = Theorie in den Biowissenschaften · 2020Article
- 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
- Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism.Journal of proteome research · 2019Article
- Constitutive Androstane Receptor Differentially Regulates Bile Acid Homeostasis in Mouse Models of Intrahepatic Cholestasis.Hepatology communications · 2019Article
- Teriflunomide Is an Indirect Human Constitutive Androstane Receptor (CAR) Activator Interacting With Epidermal Growth Factor (EGF) Signaling.Frontiers in pharmacology · 2018Article
- Crosstalk between Receptor and Non-receptor Mediated Chemical Modes of Action in Rat Livers Converges through a Dysregulated Gene Expression Network at Tumor Suppressor Tp53.Frontiers in genetics · 2017Article
- Bioinformatic analysis of microRNA networks following the activation of the constitutive androstane receptor (CAR) in mouse liver.Biochimica et biophysica acta · 2016Article
- Deciphering the roles of the constitutive androstane receptor in energy metabolism.Acta pharmacologica Sinica · 2015Review
- Nuclear receptor-mediated alleviation of alcoholic fatty liver by polyphenols contained in alcoholic beverages.PloS one · 2014Article
- Molecular Interactions between NAFLD and Xenobiotic Metabolism.Frontiers in genetics · 2013Article
- Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver.PPAR research · 2012Article
- Acrolein-induced dyslipidemia and acute-phase response are independent of HMG-CoA reductase.Molecular nutrition & food research · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDetoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia.
resultsUsing gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARalpha and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet.
conclusionOur data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARalpha and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.
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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.