P. Wei, J. Zhang, M. Egan-hafley, S. Liang, and D. D. Moore, The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism, Nature, vol.407, issue.6806, pp.920-923, 2000.

B. M. Forman, I. Tzameli, H. S. Choi, J. Chen, D. Simha et al., Androstane metabolites bind to and deactivate the nuclear receptor CAR-?, Nature, vol.395, issue.6702, pp.612-615, 1998.

T. Kawamoto, T. Sueyoshi, I. Zelko, R. Moore, K. Washburn et al., Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of the CYP2B Gene, Molecular and Cellular Biology, vol.19, issue.9, pp.6318-6322, 1999.

J. Hernandez, L. Mota, and W. Baldwin, Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation, Current Pharmacogenomics and Personalized Medicine, vol.7, issue.2, pp.81-105, 2009.

D. Li, B. Mackowiak, T. G. Brayman, M. Mitchell, L. Zhang et al., Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells, Biochemical Pharmacology, vol.98, issue.1, pp.190-202, 2015.

H. Li and H. Wang, Activation of xenobiotic receptors: driving into the nucleus, Expert Opinion on Drug Metabolism & Toxicology, vol.6, issue.4, pp.409-426, 2010.

J. M. Maglich, C. M. Stoltz, B. Goodwin, D. Hawkins-brown, J. T. Moore et al., Nuclear Pregnane X Receptor and Constitutive Androstane Receptor Regulate Overlapping but Distinct Sets of Genes Involved in Xenobiotic Detoxification, Molecular Pharmacology, vol.62, issue.3, pp.638-646, 2002.

S. P. Saini, J. Sonoda, L. Xu, D. Toma, H. Uppal et al., A Novel Constitutive Androstane Receptor-Mediated and CYP3A-Independent Pathway of Bile Acid Detoxification, Molecular Pharmacology, vol.65, issue.2, pp.292-300, 2004.

J. Sugatani, K. Yamakawa, K. Yoshinari, T. Machida, H. Takagi et al., Identification of a Defect in the UGT1A1 Gene Promoter and Its Association with Hyperbilirubinemia, Biochemical and Biophysical Research Communications, vol.292, issue.2, pp.492-497, 2002.

A. Ueda, H. K. Hamadeh, H. K. Webb, Y. Yamamoto, T. Sueyoshi et al., Diverse Roles of the Nuclear Orphan Receptor CAR in Regulating Hepatic Genes in Response to Phenobarbital, Molecular Pharmacology, vol.61, issue.1, pp.1-6, 2002.

J. Locker, J. Tian, R. Carver, D. Concas, C. Cossu et al., A common set of immediate-early response genes in liver regeneration and hyperplasia, Hepatology, vol.38, issue.2, pp.314-325, 2003.

B. Dong, P. K. Saha, W. Huang, W. Chen, L. A. Abu-elheiga et al., Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease, Proceedings of the National Academy of Sciences, vol.106, issue.44, pp.18831-18836, 2009.

J. Gao, J. He, Y. Zhai, T. Wada, and W. Xie, The Constitutive Androstane Receptor Is an Anti-obesity Nuclear Receptor That Improves Insulin Sensitivity, Journal of Biological Chemistry, vol.284, issue.38, pp.25984-25992, 2009.

X. Ding, K. Lichti, I. Kim, F. J. Gonzalez, and J. L. Staudinger, Regulation of Constitutive Androstane Receptor and Its Target Genes by Fasting, cAMP, Hepatocyte Nuclear Factor ?, and the Coactivator Peroxisome Proliferator-activated Receptor ? Coactivator-1?, Journal of Biological Chemistry, vol.281, issue.36, pp.26540-26551, 2006.

C. Fujino, Y. Watanabe, S. Sanoh, H. Nakajima, N. Uramaru et al., Activation of PXR, CAR and PPAR? by pyrethroid pesticides and the effect of metabolism by rat liver microsomes, Heliyon, vol.5, issue.9, p.e02466, 2019.

T. Abe, M. Takahashi, M. Kano, Y. Amaike, C. Ishii et al., Activation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid, Archives of Toxicology, vol.91, issue.6, pp.2365-2374, 2016.

X. Cheng and C. D. Klaassen, Perfluorocarboxylic Acids Induce Cytochrome P450 Enzymes in Mouse Liver through Activation of PPAR-? and CAR Transcription Factors, Toxicological Sciences, vol.106, issue.1, pp.29-36, 2008.

K. Oshida, N. Vasani, C. Jones, T. Moore, S. Hester et al., Identification of Chemical Modulators of the Constitutive Activated Receptor (CAR) in a Gene Expression Compendium, Nuclear Receptor Signaling, vol.13, issue.1, p.nrs.13002, 2015.

C. R. Elcombe, B. M. Elcombe, J. R. Foster, S. C. Chang, D. J. Ehresman et al., Hepatocellular hypertrophy and cell proliferation in Sprague?Dawley rats from dietary exposure to potassium perfluorooctanesulfonate results from increased expression of xenosensor nuclear receptors PPAR? and CAR/PXR, Toxicology, vol.293, issue.1-3, pp.16-29, 2012.

W. S. Baldwin and J. A. Roling, A Concentration Addition Model for the Activation of the Constitutive Androstane Receptor by Xenobiotic Mixtures, Toxicological Sciences, vol.107, issue.1, pp.93-105, 2008.

M. Y. Pakharukova, M. A. Smetanina, V. I. Kaledin, V. F. Kobzev, I. V. Romanova et al., Activation of constitutive androstane receptor under the effect of hepatocarcinogenic aminoazo dyes in mouse and rat liver, Bulletin of Experimental Biology and Medicine, vol.144, issue.3, pp.338-341, 2007.

R. C. Peffer, J. G. Moggs, T. Pastoor, R. A. Currie, J. Wright et al., Mouse Liver Effects of Cyproconazole, a Triazole Fungicide: Role of the Constitutive Androstane Receptor, Toxicological Sciences, vol.99, issue.1, pp.315-325, 2007.

M. E. Wyde, S. E. Kirwan, F. Zhang, A. Laughter, H. B. Hoffman et al., Di-n-Butyl Phthalate Activates Constitutive Androstane Receptor and Pregnane X Receptor and Enhances the Expression of Steroid-Metabolizing Enzymes in the Liver of Rat Fetuses, Toxicological Sciences, vol.86, issue.2, pp.281-290, 2005.

M. E. Wyde, E. Bartolucci, A. Ueda, H. Zhang, B. Yan et al., The Environmental Pollutant 1,1-Dichloro-2,2-bis (p-chlorophenyl)ethylene Induces Rat Hepatic Cytochrome P450 2B and 3A Expression through the Constitutive Androstane Receptor and Pregnane X Receptor, Molecular Pharmacology, vol.64, issue.2, pp.474-481, 2003.

E. M. Laurenzana, D. M. Coslo, M. V. Vigilar, A. M. Roman, and C. J. Omiecinski, Activation of the Constitutive Androstane Receptor by Monophthalates, Chemical Research in Toxicology, vol.29, issue.10, pp.1651-1661, 2016.

T. Sueyoshi, T. Kawamoto, I. Zelko, P. Honkakoski, and M. Negishi, The Repressed Nuclear Receptor CAR Responds to Phenobarbital in Activating the HumanCYP2B6Gene, Journal of Biological Chemistry, vol.274, issue.10, pp.6043-6046, 1999.

J. G. Dekeyser, M. C. Stagliano, S. S. Auerbach, K. S. Prabhu, A. D. Jones et al., Di(2-ethylhexyl) phthalate Is a Highly Potent Agonist for the Human Constitutive Androstane Receptor Splice Variant CAR2, Molecular Pharmacology, vol.75, issue.5, pp.1005-1013, 2009.

P. Wei, J. Zhang, D. H. Dowhan, Y. Han, and D. D. Moore, Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response, The Pharmacogenomics Journal, vol.2, issue.2, pp.117-126, 2002.

C. C. Savary, R. Jossé, A. Bruyère, F. Guillet, M. A. Robin et al., Interactions of Endosulfan and Methoxychlor Involving CYP3A4 and CYP2B6 in Human HepaRG Cells, Drug Metabolism and Disposition, vol.42, issue.8, pp.1235-1240, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01128192

X. J. Zhang, Z. Shi, J. X. Lyv, X. He, N. A. Englert et al., Pyrene is a Novel Constitutive Androstane Receptor (CAR) Activator and Causes Hepatotoxicity by CAR, Toxicological Sciences, vol.147, issue.2, pp.436-445, 2015.

D. Blizard, T. Sueyoshi, M. Negishi, S. S. Dehal, and D. Kupfer, Mechanism of Induction of Cytochrome P450 Enzymes by the Proestrogenic Endocrine Disruptor Pesticide-Methoxychlor: Interactions of Methoxychlor Metabolites with the Constitutive Androstane Receptor System, Drug Metab. Dispos, vol.29, pp.781-785, 2001.

S. D. Prokopec, J. D. Watson, J. Lee, R. Pohjanvirta, and P. C. Boutros, Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD, Toxicol. Appl. Pharmacol, vol.284, pp.188-196, 2015.

B. Mackowiak, L. Li, C. Lynch, A. Ziman, S. Heyward et al., High-content analysis of constitutive androstane receptor (CAR) translocation identifies mosapride citrate as a CAR agonist that represses gluconeogenesis, Biochem. Pharmacol, vol.168, pp.224-236, 2019.

D. Liang, L. Li, C. Lynch, B. Diethelm-varela, M. Xia et al., DL5050, a Selective Agonist for the Human Constitutive Androstane Receptor, ACS Medicinal Chemistry Letters, vol.10, issue.7, pp.1039-1044, 2019.

L. Cerveny, L. Svecova, E. Anzenbacherova, R. Vrzal, F. Staud et al., Valproic Acid Induces CYP3A4 and MDR1 Gene Expression by Activation of Constitutive Androstane Receptor and Pregnane X Receptor Pathways, Drug Metabolism and Disposition, vol.35, issue.7, pp.1032-1041, 2007.

J. Zhang, W. Huang, S. S. Chua, P. Wei, and D. D. Moore, Modulation of Acetaminophen-Induced Hepatotoxicity by the Xenobiotic Receptor CAR, Science, vol.298, issue.5592, pp.422-424, 2002.

J. Zhang, W. Huang, M. Qatanani, R. M. Evans, and D. D. Moore, The Constitutive Androstane Receptor and Pregnane X Receptor Function Coordinately to Prevent Bile Acid-induced Hepatotoxicity, Journal of Biological Chemistry, vol.279, issue.47, pp.49517-49522, 2004.

A. K. Goetz, W. Bao, H. Ren, J. E. Schmid, D. B. Tully et al., Gene expression profiling in the liver of CD-1 mice to characterize the hepatotoxicity of triazole fungicides, Toxicology and Applied Pharmacology, vol.215, issue.3, pp.274-284, 2006.

O. Burk, K. A. Arnold, A. K. Nussler, E. Schaeffeler, E. Efimova et al., Antimalarial Artemisinin Drugs Induce Cytochrome P450 and MDR1 Expression by Activation of Xenosensors Pregnane X Receptor and Constitutive Androstane Receptor, Molecular Pharmacology, vol.67, issue.6, pp.1954-1965, 2005.

K. Swales and M. Negishi, CAR, Driving into the Future, Molecular Endocrinology, vol.18, issue.7, pp.1589-1598, 2004.

L. Li, T. Chen, J. D. Stanton, T. Sueyoshi, M. Negishi et al., The Peripheral Benzodiazepine Receptor Ligand 1-(2-Chlorophenyl-methylpropyl)-3-isoquinoline-carboxamide Is a Novel Antagonist of Human Constitutive Androstane Receptor, Molecular Pharmacology, vol.74, issue.2, pp.443-453, 2008.

C. Malaplate-armand, L. Ferrari, C. Masson, S. Visvikis-siest, H. Lambert et al., Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells, Toxicology Letters, vol.159, issue.3, pp.203-211, 2005.
URL : https://hal.archives-ouvertes.fr/hal-01999436

J. M. Pascussi, S. Gerbal-chaloin, J. M. Fabre, P. Maurel, and M. J. Vilarem, Dexamethasone Enhances Constitutive Androstane Receptor Expression in Human Hepatocytes: Consequences on Cytochrome P450 Gene Regulation, Molecular Pharmacology, vol.58, issue.6, pp.1441-1450, 2000.

M. Qatanani, P. Wei, and D. D. Moore, Alterations in the distribution and orexigenic effects of dexamethasone in CAR-null mice, Pharmacology Biochemistry and Behavior, vol.78, issue.2, pp.285-291, 2004.

C. Duret, M. Daujat-chavanieu, J. M. Pascussi, L. Pichard-garcia, P. Balaguer et al., Ketoconazole and Miconazole Are Antagonists of the Human Glucocorticoid Receptor: Consequences on the Expression and Function of the Constitutive Androstane Receptor and the Pregnane X Receptor, Molecular Pharmacology, vol.70, issue.1, pp.329-339, 2006.
URL : https://hal.archives-ouvertes.fr/inserm-00086861

W. Huang, J. Zhang, P. Wei, W. T. Schrader, and D. D. Moore, Meclizine Is an Agonist Ligand for Mouse Constitutive Androstane Receptor (CAR) and an Inverse Agonist for Human CAR, Molecular Endocrinology, vol.18, issue.10, pp.2402-2408, 2004.

T. Saussele, O. Burk, J. K. Blievernicht, K. Klein, A. Nussler et al., Selective Induction of Human Hepatic Cytochromes P450 2B6 and 3A4 by Metamizole, Clinical Pharmacology & Therapeutics, vol.82, issue.3, pp.265-274, 2007.

X. Chen, S. Maiti, J. Zhang, and G. Chen, Nuclear receptor interactions in methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1), Journal of Biochemical and Molecular Toxicology, vol.20, issue.6, pp.309-317, 2006.

Y. Shibayama, K. Ushinohama, R. Ikeda, Y. Yoshikawa, T. Motoya et al., Effect of methotrexate treatment on expression levels of multidrug resistance protein 2, breast cancer resistance protein and organic anion transporters Oat1, Oat2 and Oat3 in rats, Cancer Science, vol.97, issue.11, pp.1260-1266, 2006.

M. Murray, E. Fiala-beer, and D. Sutton, Upregulation of cytochromes P 450 2B in rat liver by orphenadrine, British Journal of Pharmacology, vol.139, issue.4, pp.787-796, 2003.

L. Li, X. Bao, Q. Y. Zhang, M. Negishi, and X. Ding, Role of CYP2B in Phenobarbital-Induced Hepatocyte Proliferation in Mice, Drug Metabolism and Disposition, vol.45, issue.8, pp.977-981, 2017.

R. A. Currie, R. C. Peffer, A. K. Goetz, C. J. Omiecinski, and J. I. Goodman, Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action, Toxicology, vol.321, pp.80-88, 2014.

J. P. Jackson, S. S. Ferguson, R. Moore, M. Negishi, and J. A. Goldstein, The Constitutive Active/Androstane Receptor Regulates Phenytoin Induction of Cyp2c29, Molecular Pharmacology, vol.65, issue.6, pp.1397-1404, 2004.

H. Wang, S. Faucette, R. Moore, T. Sueyoshi, M. Negishi et al., Human Constitutive Androstane Receptor Mediates Induction ofCYP2B6Gene Expression by Phenytoin, Journal of Biological Chemistry, vol.279, issue.28, pp.29295-29301, 2004.

J. P. Jackson, S. S. Ferguson, M. Negishi, and J. A. Goldstein, Phenytoin Induction of the Cyp2c37 Gene Is Mediated by the Constitutive Androstane Receptor, Drug Metabolism and Disposition, vol.34, issue.12, pp.2003-2010, 2006.

K. Howe, F. Sanat, A. E. Thumser, T. Coleman, and N. Plant, The statin class of HMG-CoA reductase inhibitors demonstrate differential activation of the nuclear receptors PXR, CAR and FXR, as well as their downstream target genes, Xenobiotica, vol.41, issue.7, pp.519-529, 2011.

T. Re?en, M. Hafner, S. Kortagere, S. Ekins, V. Hodnik et al., Rosuvastatin and Atorvastatin Are Ligands of the Human Constitutive Androstane Receptor/Retinoid X Receptor ? Complex, Drug Metabolism and Disposition, vol.45, issue.8, pp.974-976, 2017.

J. Sugatani, H. Kojima, A. Ueda, S. Kakizaki, K. Yoshinari et al., The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR, Hepatology, vol.33, issue.5, pp.1232-1238, 2001.

G. L. Guo, S. Choudhuri, and C. D. Klaassen, Induction Profile of Rat Organic Anion Transporting Polypeptide 2 (oatp2) by Prototypical Drug-Metabolizing Enzyme Inducers That Activate Gene Expression through Ligand-Activated Transcription Factor Pathways, Journal of Pharmacology and Experimental Therapeutics, vol.300, issue.1, pp.206-212, 2002.

J. M. Ridlon, D. J. Kang, and P. B. Hylemon, Bile salt biotransformations by human intestinal bacteria, Journal of Lipid Research, vol.47, issue.2, pp.241-259, 2005.

L. D. Beilke, L. M. Aleksunes, R. D. Holland, D. G. Besselsen, R. D. Beger et al., Constitutive Androstane Receptor-Mediated Changes in Bile Acid Composition Contributes to Hepatoprotection from Lithocholic Acid-Induced Liver Injury in Mice, Drug Metabolism and Disposition, vol.37, issue.5, pp.1035-1045, 2009.

J. B. Schenkman, Steroid metabolism by constitutive cytochromes P450, The Journal of Steroid Biochemistry and Molecular Biology, vol.43, issue.8, pp.1023-1030, 1992.

Y. Yamamoto, R. Moore, H. A. Hess, G. L. Guo, F. J. Gonzalez et al., Estrogen Receptor ? Mediates 17?-Ethynylestradiol Causing Hepatotoxicity, Journal of Biological Chemistry, vol.281, issue.24, pp.16625-16631, 2006.

T. Sueyoshi, W. D. Green, K. Vinal, T. S. Woodrum, R. Moore et al., Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver, PLoS ONE, vol.6, issue.6, p.e21229, 2011.

P. G. Curran and L. J. Degroot, The Effect of Hepatic Enzyme-Inducing Drugs on Thyroid Hormones and the Thyroid Gland*, Endocrine Reviews, vol.12, issue.2, pp.135-150, 1991.

M. Qatanani, J. Zhang, and D. D. Moore, Role of the Constitutive Androstane Receptor in Xenobiotic-Induced Thyroid Hormone Metabolism, Endocrinology, vol.146, issue.3, pp.995-1002, 2005.

T. J. Visser, E. Kaptein, H. Glatt, I. Bartsch, M. Hagen et al., Characterization of thyroid hormone sulfotransferases, Chemico-Biological Interactions, vol.109, issue.1-3, pp.279-291, 1998.

C. Lukowicz, S. Ellero-simatos, M. Régnier, F. Oliviero, F. Lasserre et al., Dimorphic metabolic and endocrine disorders in mice lacking the constitutive androstane receptor, Scientific Reports, vol.9, issue.1, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02627769

N. Wieneke, K. I. Hirsch-ernst, M. Kuna, S. Kersten, and G. P. Püschel, PPAR?-dependent induction of the energy homeostasis-regulating nuclear receptor NR1i3 (CAR) in rat hepatocytes: Potential role in starvation adaptation, FEBS Letters, vol.581, issue.29, pp.5617-5626, 2007.

J. M. Pascussi, M. Busson-le-coniat, P. Maurel, and M. J. Vilarem, Transcriptional Analysis of the Orphan Nuclear Receptor Constitutive Androstane Receptor (NR1I3) Gene Promoter: Identification of a Distal Glucocorticoid Response Element, Molecular Endocrinology, vol.17, issue.1, pp.42-55, 2003.

J. T. Lahtela, A. J. Arranto, and E. A. Sotaniemi, Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects, Diabetes, vol.34, pp.911-916, 1985.

E. A. Sotaniemi, A. J. Arranto, S. Sutinen, J. H. Stengård, and S. Sutinen, Treatment of noninsulin-dependent diabetes mellitus with enzyme inducers, Clin. Pharmacol. Ther, vol.33, pp.826-835, 1983.

S. Kodama, C. Koike, M. Negishi, and Y. Yamamoto, Nuclear Receptors CAR and PXR Cross Talk with FOXO1 To Regulate Genes That Encode Drug-Metabolizing and Gluconeogenic Enzymes, Molecular and Cellular Biology, vol.24, issue.18, pp.7931-7940, 2004.

J. Miao, S. Fang, Y. Bae, and J. K. Kemper, Functional Inhibitory Cross-talk between Constitutive Androstane Receptor and Hepatic Nuclear Factor-4 in Hepatic Lipid/Glucose Metabolism Is Mediated by Competition for Binding to the DR1 Motif and to the Common Coactivators, GRIP-1 and PGC-1?, Journal of Biological Chemistry, vol.281, issue.21, pp.14537-14546, 2006.

J. Gao, J. Yan, M. Xu, S. Ren, and W. Xie, CAR Suppresses Hepatic Gluconeogenesis by Facilitating the Ubiquitination and Degradation of PGC1?, Molecular Endocrinology, vol.29, issue.11, pp.1558-1570, 2015.

X. Shi, Q. Cheng, L. Xu, J. Yan, M. Jiang et al., Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4, Molecular and Cellular Biology, vol.34, issue.3, pp.485-497, 2013.

C. Lynch, Y. Pan, L. Li, S. Heyward, T. Moeller et al., Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes, Toxicology and Applied Pharmacology, vol.279, issue.1, pp.33-42, 2014.

C. Breuker, A. Moreau, L. Lakhal, V. Tamasi, Y. Parmentier et al., Hepatic Expression of Thyroid Hormone-Responsive Spot 14 Protein Is Regulated by Constitutive Androstane Receptor (NR1I3), Endocrinology, vol.151, issue.4, pp.1653-1661, 2010.

A. Marmugi, C. Lukowicz, F. Lasserre, A. Montagner, A. Polizzi et al., Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way, Toxicology and Applied Pharmacology, vol.303, pp.90-100, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01837194

C. La-vecchia and E. Negri, A review of epidemiological data on epilepsy, phenobarbital, and risk of liver cancer, European Journal of Cancer Prevention, vol.23, issue.1, pp.1-7, 2014.

A. Verrotti, S. Agostinelli, P. Parisi, F. Chiarelli, and G. Coppola, Nonalcoholic fatty liver disease in adolescents receiving valproic acid, Epilepsy & Behavior, vol.20, issue.2, pp.382-385, 2011.

A. Kassam, C. J. Winrow, F. Fernandez-rachubinski, J. P. Capone, and R. A. Rachubinski, The Peroxisome Proliferator Response Element of the Gene Encoding the Peroxisomal ?-Oxidation Enzyme Enoyl-CoA Hydratase/3-Hydroxyacyl-CoA Dehydrogenase Is a Target for Constitutive Androstane Receptor ?/9-cis-Retinoic Acid Receptor-mediated Transactivation, Journal of Biological Chemistry, vol.275, issue.6, pp.4345-4350, 2000.

W. Chen, G. Chen, D. L. Head, D. J. Mangelsdorf, and D. W. Russell, Enzymatic Reduction of Oxysterols Impairs LXR Signaling in Cultured Cells and the Livers of Mice, Cell Metabolism, vol.5, issue.1, pp.73-79, 2007.

M. Lee, J. T. Hwang, H. Lee, S. N. Jung, I. Kang et al., AMP-activated Protein Kinase Activity Is Critical for Hypoxia-inducible Factor-1 Transcriptional Activity and Its Target Gene Expression under Hypoxic Conditions in DU145 Cells, Journal of Biological Chemistry, vol.278, issue.41, pp.39653-39661, 2003.

G. M. Hudson, K. L. Flannigan, S. L. Erickson, F. A. Vicentini, A. Zamponi et al., Constitutive androstane receptor regulates the intestinal mucosal response to injury, British Journal of Pharmacology, vol.174, issue.12, pp.1857-1871, 2017.

J. L. Dempsey, D. Wang, G. Siginir, Q. Fei, D. Raftery et al., Pharmacological Activation of PXR and CAR Downregulates Distinct Bile Acid-Metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis, Toxicological Sciences, vol.168, issue.1, pp.40-60, 2018.

M. Little, M. Dutta, H. Li, A. Matson, X. Shi et al., Understanding the Physiological Functions of the Host Xenobiotic-sensing Nuclear Receptors PXR and CAR on the Gut Microbiome using Genetically Modified Mice, 2020.

Y. J. Choi, D. Zhou, A. C. Barbosa, Y. Niu, X. Guan et al., Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia-Reperfusion?Induced Kidney and Liver Injury, Molecular Pharmacology, vol.93, issue.3, pp.239-250, 2018.

E. Roh and M. S. Kim, Brain Regulation of Energy Metabolism, Endocrinology and Metabolism, vol.31, issue.4, p.519, 2016.

P. Giannoni, J. Badaut, C. Dargazanli, A. F. De-maudave, W. Klement et al., The pericyte?glia interface at the blood?brain barrier, Clinical Science, vol.132, issue.3, pp.361-374, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02074159

P. Giannoni, S. Claeysen, F. Noe, and N. Marchi, Peripheral Routes to Neurodegeneration: Passing Through the Blood?Brain Barrier, Frontiers in Aging Neuroscience, vol.12, 2020.
URL : https://hal.archives-ouvertes.fr/hal-02465771

M. D. Sweeney, Z. Zhao, A. Montagne, A. R. Nelson, and B. V. Zlokovic, Blood-Brain Barrier: From Physiology to Disease and Back, Physiological Reviews, vol.99, issue.1, pp.21-78, 2019.

N. J. Abbott, A. A. Patabendige, D. E. Dolman, S. R. Yusof, and D. J. Begley, Structure and function of the blood?brain barrier, Neurobiology of Disease, vol.37, issue.1, pp.13-25, 2010.

M. Nishimura, S. Naito, and T. Yokoi, Tissue-specific mRNA Expression Profiles of Human Nuclear Receptor Subfamilies, Drug Metabolism and Pharmacokinetics, vol.19, issue.2, pp.135-149, 2004.

J. K. Lamba, V. K. Lamba, K. Yasuda, Y. S. Lin, M. Assem et al., Expression of Constitutive Androstane Receptor Splice Variants in Human Tissues and Their Functional Consequences, Journal of Pharmacology and Experimental Therapeutics, vol.311, issue.2, pp.811-821, 2004.

F. Dutheil, S. Dauchy, M. Diry, V. Sazdovitch, O. Cloarec et al., Xenobiotic-Metabolizing Enzymes and Transporters in the Normal Human Brain: Regional and Cellular Mapping as a Basis for Putative Roles in Cerebral Function, Drug Metabolism and Disposition, vol.37, issue.7, pp.1528-1538, 2009.

M. Souidi, Y. Gueguen, C. Linard, N. Dudoignon, S. Grison et al., In vivo effects of chronic contamination with depleted uranium on CYP3A and associated nuclear receptors PXR and CAR in the rat, Toxicology, vol.214, issue.1-2, pp.113-122, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00405243

S. Marini, A. Nannelli, D. Sodini, S. Dragoni, M. Valoti et al., Expression, microsomal and mitochondrial activities of cytochrome P450 enzymes in brain regions from control and phenobarbital-treated rabbits, Life Sciences, vol.80, issue.10, pp.910-917, 2007.

M. Kajta, A. Wnuk, J. Rzemieniec, W. Lason, M. Mackowiak et al., Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis, Molecular Neurobiology, vol.56, issue.5, pp.3113-3131, 2018.

E. Litwa, J. Rzemieniec, A. Wnuk, W. Lason, W. Krzeptowski et al., RXR?, PXR and CAR xenobiotic receptors mediate the apoptotic and neurotoxic actions of nonylphenol in mouse hippocampal cells, The Journal of Steroid Biochemistry and Molecular Biology, vol.156, pp.43-52, 2016.

, Table S6: List of identified proteins in the EV proteome that overlap with the Brain protein atlas protein list downloaded from Human protein atlas, The Human Protein Atlas

B. Weksler, I. A. Romero, and P. O. Couraud, The hCMEC/D3 cell line as a model of the human blood brain barrier, Fluids and Barriers of the CNS, vol.10, issue.1, p.16, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00812147

H. Wang and E. L. Lecluyse, Role of Orphan Nuclear Receptors in the Regulation of Drug-Metabolising Enzymes, Clinical Pharmacokinetics, vol.42, issue.15, pp.1331-1357, 2003.

D. S. Miller, Regulation of ABC Transporters Blood?Brain Barrier, ABC Transporters and Cancer, vol.125, pp.43-70, 2015.

G. N. Chan, M. T. Hoque, C. L. Cummins, and R. Bendayan, Regulation of P-glycoprotein by orphan nuclear receptors in human brain microvessel endothelial cells, Journal of Neurochemistry, vol.118, issue.2, pp.163-175, 2011.

X. Wang, D. B. Sykes, and D. S. Miller, Constitutive Androstane Receptor-Mediated Up-Regulation of ATP-Driven Xenobiotic Efflux Transporters at the Blood-Brain Barrier, Molecular Pharmacology, vol.78, issue.3, pp.376-383, 2010.

L. M. Slosky, B. J. Thompson, L. Sanchez-covarrubias, Y. Zhang, M. L. Laracuente et al., Acetaminophen Modulates P-Glycoprotein Functional Expression at the Blood-Brain Barrier by a Constitutive Androstane Receptor?Dependent Mechanism, Molecular Pharmacology, vol.84, issue.5, pp.774-786, 2013.

V. K. Tripathi, V. Kumar, A. Pandey, P. Vatsa, A. Dhasmana et al., Monocrotophos Induces the Expression of Xenobiotic Metabolizing Cytochrome P450s (CYP2C8 and CYP3A4) and Neurotoxicity in Human Brain Cells, Molecular Neurobiology, vol.54, issue.5, pp.3633-3651, 2016.

C. Ghosh, V. Puvenna, J. Gonzalez-martinez, D. Janigro, and N. Marchi, Blood-Brain Barrier P450 Enzymes and Multidrug Transporters in Drug Resistance: A Synergistic Role in Neurological Diseases, Current Drug Metabolism, vol.12, issue.8, pp.742-749, 2011.

S. Chakraborty, S. Kanakasabai, and J. J. Bright, Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells, British Journal of Cancer, vol.104, issue.3, pp.448-459, 2011.

J. M. Maglich, D. J. Parks, L. B. Moore, J. L. Collins, B. Goodwin et al., Identification of a Novel Human Constitutive Androstane Receptor (CAR) Agonist and Its Use in the Identification of CAR Target Genes, Journal of Biological Chemistry, vol.278, issue.19, pp.17277-17283, 2003.

J. Lemmen, I. E. Tozakidis, P. Bele, and H. J. Galla, Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood?brain barrier after CITCO activation, Brain Research, vol.1501, pp.68-80, 2013.

T. S. Koemans, T. Kleefstra, M. C. Chubak, M. H. Stone, M. R. Reijnders et al., Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder, PLOS Genetics, vol.13, issue.10, p.e1006864, 2017.

B. Boussadia, G. Gangarossa, L. Mselli-lakhal, M. Rousset, F. De-bock et al., Lack of CAR impacts neuronal function and cerebrovascular integrity in vivo, Experimental Neurology, vol.283, pp.39-48, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02641172

P. Torres?vergara, Y. S. Ho, F. Espinoza, F. Nualart, C. Escudero et al., The constitutive androstane receptor and pregnane X receptor in the brain, British Journal of Pharmacology, vol.177, issue.12, pp.2666-2682, 2020.

T. L. Davidson, A. Monnot, A. U. Neal, A. A. Martin, J. J. Horton et al., The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood?brain barrier integrity differ for diet-induced obese and diet-resistant rats, Physiology & Behavior, vol.107, issue.1, pp.26-33, 2012.

J. M. Ferro, S. N. Oliveira, and L. Correia, Neurologic manifestations of inflammatory bowel diseases, Neurologic Aspects of Systemic Disease Part II, pp.595-605, 2014.

B. V. Elsevier, , vol.120, pp.595-605, 2014.

G. Casella, V. Villanacci, L. Vicentini, V. Baldini, and G. Bassotti, Primary Hyperpara-Thyroidism Associated with Ulcerative Colitis, Inflammatory Bowel Diseases, vol.19, issue.3, pp.E40-E41, 2013.

W. Miehsler, W. Reinisch, E. Valic, W. Osterode, W. Tillinger et al., Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?, Gut, vol.53, issue.4, pp.542-548, 2004.

A. Varatharaj and I. Galea, The blood-brain barrier in systemic inflammation, Brain, Behavior, and Immunity, vol.60, pp.1-12, 2017.

K. Duszka and W. Wahli, Enteric Microbiota?Gut?Brain Axis from the Perspective of Nuclear Receptors, International Journal of Molecular Sciences, vol.19, issue.8, p.2210, 2018.