Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes

Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

Volumn 1859, Issue 9, 2016, Pages 1218-1227

  Kandel, Benjamin A ^a,b   Thomas, Maria ^a,b   Winter, Stefan ^a,b   Damm, Georg ^c   Seehofer, Daniel ^c   Burk, Oliver ^a,b   Schwab, Matthias ^a,b   Zanger, Ulrich M ^a,b  

^a DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^b UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Cytochrome P450; Drug metabolism; Microarray; Nuclear receptors; Primary human hepatocytes; Transcriptome

Indexed keywords

6 (4 CHLOROPHENYL)IMIDAZO[2,1 B][1,3]THIAZOLE 5 CARBALDEHYDE O (3,4 DICHLOROBENZYL)OXIME; CHIMERIC ANTIGEN RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PIRINIXIC ACID; PREGNANE X RECEPTOR; RIFAMPICIN; TRANSCRIPTOME; UNCLASSIFIED DRUG; XENOBIOTIC AGENT; 6-(4-CHLOROPHENYL)IMIDAZO(2,1-B)(1,3)THIAZOLE-5-CARBALDEHYDE O-(3,4-DICHLOROBENZYL)OXIME; CELL RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CYTOCHROME P450; LIGAND; OXIME; PYRIMIDINE DERIVATIVE; STEROID RECEPTOR; THIAZOLE DERIVATIVE;

ADULT; AGED; ARTICLE; CELL CULTURE; CLINICAL ARTICLE; COMPARATIVE GENE MAPPING; COMPARATIVE STUDY; CONTROLLED STUDY; DOWN REGULATION; FEMALE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE IDENTIFICATION; GENE INDUCTION; HUMAN; HUMAN CELL; LIVER CELL; MALE; MICROARRAY ANALYSIS; MIDDLE AGED; PRIORITY JOURNAL; PROTEIN FUNCTION; RNA ANALYSIS; UPREGULATION; AGONISTS; CYTOLOGY; DRUG EFFECTS; DRUG INACTIVATION; GENE EXPRESSION PROFILING; GENE ONTOLOGY; GENETICS; GENOME-WIDE ASSOCIATION STUDY; METABOLISM; MOLECULAR GENETICS; PRIMARY CELL CULTURE; SIGNAL TRANSDUCTION;

ADULT; CYTOCHROME P-450 ENZYME SYSTEM; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE ONTOLOGY; GENOME-WIDE ASSOCIATION STUDY; HEPATOCYTES; HUMANS; INACTIVATION, METABOLIC; LIGANDS; MALE; METABOLIC NETWORKS AND PATHWAYS; MIDDLE AGED; MOLECULAR SEQUENCE ANNOTATION; OXIMES; PPAR ALPHA; PRIMARY CELL CULTURE; PYRIMIDINES; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID; RIFAMPIN; SIGNAL TRANSDUCTION; THIAZOLES; TRANSCRIPTOME;

EID: 84963813234     PISSN: 18749399     EISSN: 18764320     Source Type: Journal    
DOI: 10.1016/j.bbagrm.2016.03.007     Document Type: Article

References (71)

1. [1] Ambroise, J., Bearzatto, B., Robert, A., Govaerts, B., Macq, B., Gala, J.-L., Impact of the spotted microarray preprocessing method on fold-change compression and variance stability. BMC Bioinf., 12, 2011, 413, 10.1186/1471-2105-12-413.
2. [2] Becnel, L.B., Darlington, Y.F., Ochsner, S.A., Easton-Marks, J.R., Watkins, C.M., McOwiti, A., et al. Nuclear receptor signaling atlas: opening access to the biology of nuclear receptor signaling pathways. PLoS One, 10, 2015, 10.1371/journal.pone.0135615.
3. [3] Bertilsson, G., Berkenstam, A., Blomquist, P., Functionally conserved xenobiotic responsive enhancer in cytochrome P450 3A7. Biochem. Biophys. Res. Commun. 280 (2001), 139–144, 10.1006/bbrc.2000.4066.
4. [4] Bitter, A., Nüssler, A.K., Thasler, W.E., Klein, K., Zanger, U.M., Schwab, M., et al. Human sterol regulatory element-binding protein 1a contributes significantly to hepatic lipogenic gene expression. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 35 (2015), 803–815, 10.1159/000369739.
5. [5] Bitter, A., Rümmele, P., Klein, K., Kandel, B.A., Rieger, J.K., Nüssler, A.K., et al. Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms. Arch. Toxicol. 89 (2015), 2089–2103, 10.1007/s00204-014-1348-x.
6. [6] Braeuning, A., Thomas, M., Hofmann, U., Vetter, S., Zeller, E., Petzuch, B., et al. Comparative analysis and functional characterization of hc-afw1 hepatocarcinoma cells: cytochrome P450 expression and induction by nuclear receptor agonists. Drug Metab. Dispos. 43 (2015), 1781–1787, 10.1124/dmd.115.064667.
7. [7] Burk, O., Koch, I., Raucy, J., Hustert, E., Eichelbaum, M., Brockmöller, J., et al. The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). J. Biol. Chem. 279 (2004), 38379–38385, 10.1074/jbc.M404949200.
8. [8] Burk, O., Tegude, H., Koch, I., Hustert, E., Wolbold, R., Glaeser, H., et al. Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine. J. Biol. Chem. 277 (2002), 24280–24288, 10.1074/jbc.M202345200.
9. [9] Chaudhry, A.S., Thirumaran, R.K., Yasuda, K., Yang, X., Fan, Y., Strom, S.C., et al. Genetic variation in aldo-keto reductase 1d1 (akr1d1) affects the expression and activity of multiple cytochrome P450s. Drug Metab. Dispos. 41 (2013), 1538–1547, 10.1124/dmd.113.051672.
10. [10] Chen, Y., Goldstein, J.A., The transcriptional regulation of the human CYP2C genes. Curr. Drug Metab. 10 (2009), 567–578.
11. [11] Cui, J.Y., Gunewardena, S.S., Rockwell, C.E., Klaassen, C.D., ChIPing the cistrome of PXR in mouse liver. Nucleic Acids Res. 38 (2010), 7943–7963, 10.1093/nar/gkq654.
12. [12] van Dijk, R., Kremer, A.E., Smit, W., van den Elzen, B., van Gulik, T., Gouma, D., et al. Characterization and treatment of persistent hepatocellular secretory failure. Liver Int. Off. J. Int. Assoc. Study Liver 35 (2015), 1478–1488, 10.1111/liv.12603.
13. [13] Edgar, R., Domrachev, M., Lash, A.E., Gene expression omnibus: ncbi gene expression and hybridization array data repository. Nucleic Acids Res. 30 (2002), 207–210.
14. [14] Feuer, R., Vlaic, S., Arlt, J., Sawodny, O., Dahmen, U., Zanger, U.M., et al. Lemming: a linear error model to normalize parallel quantitative real-time pcr (qpcr) data as an alternative to reference gene based methods. PLoS One, 10, 2015, e0135852, 10.1371/journal.pone.0135852.
15. [15] Gao, J., Xie, W., Targeting xenobiotic receptors PXR and CAR for metabolic diseases. Trends Pharmacol. Sci., 2012, 10.1016/j.tips.2012.07.003.
16. [16] Gellner, K., Eiselt, R., Hustert, E., Arnold, H., Koch, I., Haberl, M., et al. Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics 11 (2001), 111–121.
17. [17] Gerbal-Chaloin, S., Iankova, I., Maurel, P., Daujat-Chavanieu, M., Nuclear receptors in the cross-talk of drug metabolism and inflammation. Drug Metab. Rev. 45 (2013), 122–144, 10.3109/03602532.2012.756011.
18. [18] Ghonem, N.S., Ananthanarayanan, M., Soroka, C.J., Boyer, J.L., Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion. Hepatology 59 (2014), 1030–1042, 10.1002/hep.26894.
19. [19] Godoy, P., Hewitt, N.J., Albrecht, U., Andersen, M.E., Ansari, N., Bhattacharya, S., et al. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch. Toxicol. 87 (2013), 1315–1530, 10.1007/s00204-013-1078-5.
20. [20] Goodwin, B., Hodgson, E., D'Costa, D.J., Robertson, G.R., Liddle, C., Transcriptional regulation of the human cyp3a4gene by the constitutive androstane receptor. Mol. Pharmacol. 62 (2002), 359–365, 10.1124/mol.62.2.359.
21. [21] Goodwin, B., Moore, L.B., Stoltz, C.M., McKee, D.D., Kliewer, S.A., Regulation of the human Cyp2b6 gene by the nuclear pregnane X receptor. Mol. Pharmacol. 60 (2001), 427–431.
22. [22] Gotoh, S., Negishi, M., Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis. Sci. Rep., 5, 2015, 10.1038/srep14076.
23. [23] Guzelian, J., Barwick, J.L., Hunter, L., Phang, T.L., Quattrochi, L.C., Guzelian, P.S., Identification of genes controlled by the pregnane X receptor by microarray analysis of mrnas from pregnenolone 16α-carbonitrile treated rats. Toxicol. Sci. Off. J. Soc. Toxicol. 94 (2006), 379–387, 10.1093/toxsci/kfl116.
24. [24] Hafner, M., Juvan, P., Rezen, T., Monostory, K., Pascussi, J.-M., Rozman, D., The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action. Pharmacogenet. Genomics 21 (2011), 741–750, 10.1097/FPC.0b013e32834a5585.
25. [25] Hariparsad, N., Chu, X., Yabut, J., Labhart, P., Hartley, D.P., Dai, X., et al. Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes. Nucleic Acids Res. 37 (2009), 1160–1173, 10.1093/nar/gkn1047.
26. [26] Huang, D.W., Sherman, B.T., Lempicki, R.A., Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4 (2009), 44–57, 10.1038/nprot.2008.211.
27. [27] Hukkanen, J., Hakkola, J., Rysä, J., Pregnane X receptor (PXR)–a contributor to the diabetes epidemic?. Drug Metabol. Drug Interact. 29 (2014), 3–15, 10.1515/dmdi-2013-0036.
28. [28] Itoh, M., Nakajima, M., Higashi, E., Yoshida, R., Nagata, K., Yamazoe, Y., et al. Induction of human CYP2A6 is mediated by the pregnane X receptor with peroxisome proliferator-activated receptor-gamma coactivator 1alpha. J. Pharmacol. Exp. Ther. 319 (2006), 693–702, 10.1124/jpet.106.107573.
29. [29] Jansen, S., Cashman, K., Thompson, J.G., Pantaleon, M., Kaye, P.L., Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-alpha (PPARA) cause peroxisome proliferation in preimplantation mouse embryos. Reprod. Camb. Engl. 138 (2009), 493–505, 10.1530/REP-09-0038.
30. [30] Janssen, A.W.F., Betzel, B., Stoopen, G., Berends, F.J., Janssen, I.M., Peijnenburg, A.A., et al. The impact of PPARα activation on whole genome gene expression in human precision cut liver slices. BMC Genomics, 16, 2015, 760, 10.1186/s12864-015-1969-3.
31. [31] Kersten, S., Integrated physiology and systems biology of PPARα. Mol. Metab. 3 (2014), 354–371, 10.1016/j.molmet.2014.02.002.
32. [32] Klein, M., Thomas, M., Hofmann, U., Seehofer, D., Damm, G., Zanger, U.M., A systematic comparison of the impact of inflammatory signaling on absorption, distribution, metabolism, and excretion gene expression and activity in primary human hepatocytes and HepaRG cells. Drug Metab. Dispos. Biol. Fate Chem. 43 (2015), 273–283, 10.1124/dmd.114.060962.
33. [33] Kodama, S., Hosseinpour, F., Goldstein, J.A., Negishi, M., Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure. Nucleic Acids Res. 39 (2011), 8392–8403, 10.1093/nar/gkr458.
34. [34] Kodama, S., Moore, R., Yamamoto, Y., Negishi, M., Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene. Biochem. J. 407 (2007), 373–381, 10.1042/BJ20070481.
35. [35] Kodama, S., Negishi, M., PXR cross-talks with internal and external signals in physiological and pathophysiological responses. Drug Metab. Rev. 45 (2013), 300–310, 10.3109/03602532.2013.795585.
36. [36] Konno, Y., Negishi, M., Kodama, S., The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. Drug Metab. Pharmacokinet. 23 (2008), 8–13.
37. [37] Lambert, C.B., Spire, C., Claude, N., Guillouzo, A., Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol. Appl. Pharmacol. 234 (2009), 345–360, 10.1016/j.taap.2008.11.008.
38. [38] Lefebvre, P., Benomar, Y., Staels, B., Retinoid X receptors: common heterodimerization partners with distinct functions. Trends Endocrinol. Metab. 21 (2010), 676–683, 10.1016/j.tem.2010.06.009.
39. [39] Li, D., Mackowiak, B., Brayman, T.G., Mitchell, M., Zhang, L., Huang, S.-M., et al. Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells. Biochem. Pharmacol. 98 (2015), 190–202, 10.1016/j.bcp.2015.08.087.
40. [40] Li, T., Chiang, J.Y.L., Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription. Am. J. Physiol. Gastrointest. Liver Physiol. 288 (2005), G74–G84, 10.1152/ajpgi.00258.2004.
41. [41] Lynch, C., Zhao, J., Huang, R., Xiao, J., Li, L., Heyward, S., et al. Quantitative high-throughput identification of drugs as modulators of human constitutive androstane receptor. Sci. Rep., 5, 2015, 10.1038/srep10405.
42. [42] Maglich, J.M., Parks, D.J., Moore, L.B., Collins, J.L., Goodwin, B., Billin, A.N., et al. Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J. Biol. Chem. 278 (2003), 17277–17283, 10.1074/jbc.M300138200.
43. [43] Makia, N.L., Goldstein, J.A., Cyp2c8 is a novel target of peroxisome proliferator-activated α(PPARα) in human liver. Mol. Pharmacol., 2015, 10.1124/mol.115.100255.
44. [44] Mandard, S., Stienstra, R., Escher, P., Tan, N.S., Kim, I., Gonzalez, F.J., et al. Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors. Cell. Mol. Life Sci. 64 (2007), 1145–1157, 10.1007/s00018-007-7006-1.
45. [45] McMullen, P.D., Bhattacharya, S., Woods, C.G., Sun, B., Yarborough, K., Ross, S.M., et al. A map of the PPARα transcription regulatory network for primary human hepatocytes. Chem. Biol. Interact., 2013, 10.1016/j.cbi.2013.11.006.
46. [46] Miao, J., Fang, S., Bae, Y., Kemper, J.K., 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-1alpha. J. Biol. Chem. 281 (2006), 14537–14546, 10.1074/jbc.M510713200.
47. [47] Moore, L.B., Parks, D.J., Jones, S.A., Bledsoe, R.K., Consler, T.G., Stimmel, J.B., et al. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J. Biol. Chem. 275 (2000), 15122–15127.
48. [48] Moreau, A., Téruel, C., Beylot, M., Albalea, V., Tamasi, V., Umbdenstock, T., et al. A novel pregnane X receptor and S14-mediated lipogenic pathway in human hepatocyte. Hepatology 49 (2009), 2068–2079, 10.1002/hep.22907.
49. [49] Moreau, A., Vilarem, M.J., Maurel, P., Pascussi, J.M., Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol. Pharm. 5 (2008), 35–41, 10.1021/mp700103m.
50. [50] Mutoh, S., Sobhany, M., Moore, R., Perera, L., Pedersen, L., Sueyoshi, T., et al. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling. Sci. Signal., 6, 2013, ra31, 10.1126/scisignal.2003705.
51. [51] Nakamura, K., Moore, R., Negishi, M., Sueyoshi, T., Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver. J. Biol. Chem. 282 (2007), 9768–9776, 10.1074/jbc.M610072200.
52. [52] Page, J.L., Johnson, M.C., Olsavsky, K.M., Strom, S.C., Zarbl, H., Omiecinski, C.J., Gene expression profiling of extracellular matrix as an effector of human hepatocyte phenotype in primary cell culture. Toxicol. Sci. 97 (2007), 384–397, 10.1093/toxsci/kfm034.
53. [53] Pawlak, M., Lefebvre, P., Staels, B., General molecular biology and architecture of nuclear receptors. Curr. Top. Med. Chem., 2012 (Available at: http://www.ncbi.nlm.nih.gov/pubmed/22242852 [Accessed January 19, 2012]).
54. [54] Podvinec, M., Handschin, C., Looser, R., Meyer, U.A., Identification of the xenosensors regulating human 5-aminolevulinate synthase. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 9127–9132, 10.1073/pnas.0401845101.
55. [55] Pyper, S.R., Viswakarma, N., Yu, S., Reddy, J.K., PPARalpha: energy combustion, hypolipidemia, inflammation and cancer. Nucl. Recept. Signal., 8, 2010, e002, 10.1621/nrs.08002.
56. [56] Rakhshandehroo, M., Hooiveld, G., Müller, M., Kersten, S., Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One, 4, 2009, e6796, 10.1371/journal.pone.0006796.
57. [57] Rižner, T.L., Penning, T.M., Role of aldo-keto reductase family 1 (akr1) enzymes in human steroid metabolism. Steroids, 79, 2014, 10.1016/j.steroids.2013.10.012.
58. [58] Rosenfeld, J.M., Vargas, R., Xie, W., Evans, R.M., Genetic profiling defines the xenobiotic gene network controlled by the nuclear receptor pregnane X receptor. Mol. Endocrinol. Baltim. Md 17 (2003), 1268–1282, 10.1210/me.2002-0421.
59. [59] Rysä, J., Buler, M., Savolainen, M.J., Ruskoaho, H., Hakkola, J., Hukkanen, J., Pregnane X receptor agonists impair postprandial glucose tolerance. Clin. Pharmacol. Ther. 93 (2013), 556–563, 10.1038/clpt.2013.48.
60. [60] Tao, R., Xiong, X., Harris, R.A., White, M.F., Dong, X.C., Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes. PLoS One, 8, 2013, e71997, 10.1371/journal.pone.0071997.
61. [61] Thomas, M., Burk, O., Klumpp, B., Kandel, B.A., Damm, G., Weiss, T.S., et al. Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor alpha (PPARα). Mol. Pharmacol. 83 (2013), 709–718, 10.1124/mol.112.082503.
62. [62] Thomas, M., Winter, S., Klumpp, B., Turpeinen, M., Klein, K., Schwab, M., et al. Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8. Pharmacogenet. Pharmacogenomics, 6, 2015, 261, 10.3389/fphar.2015.00261.
63. [63] Tojima, H., Kakizaki, S., Yamazaki, Y., Takizawa, D., Horiguchi, N., Sato, K., et al. Ligand dependent hepatic gene expression profiles of nuclear receptors CAR and PXR. Toxicol. Lett. 212 (2012), 288–297, 10.1016/j.toxlet.2012.06.001.
64. [64] Ueda, A., Hamadeh, H.K., Webb, H.K., Yamamoto, Y., Sueyoshi, T., Afshari, C.A., et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol. Pharmacol. 61 (2002), 1–6.
65. [65] Wada, T., Gao, J., Xie, W., PXR and CAR in energy metabolism. Trends Endocrinol. Metab. 20 (2009), 273–279, 10.1016/j.tem.2009.03.003.
66. [66] Wang, H., Faucette, S., Sueyoshi, T., Moore, R., Ferguson, S., Negishi, M., et al. A novel distal enhancer module regulated by pregnane X receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression. J. Biol. Chem. 278 (2003), 14146–14152, 10.1074/jbc.M212482200.
67. [67] Xie, W (Ed) (2009): Nuclear Receptors In Drug Metabolism. John Wiley & Sons, Inc., Hoboken, NJ, USA. ISBN 978–0-470-08679-7.
68. [68] Xu, S., Sun, A.-Q., Suchy, F.J., A novel RARα/CAR-mediated mechanism for regulation of human organic solute transporter-β gene expression. Am. J. Physiol. Gastrointest. Liver Physiol. 306 (2014), G154–G162, 10.1152/ajpgi.00138.2013.
69. [69] Yang, H., Wang, H., Signaling control of the constitutive androstane receptor (CAR). Protein Cell 5 (2014), 113–123, 10.1007/s13238–013-0013-0.
70. [70] Yoshinari, K., Yoda, N., Toriyabe, T., Yamazoe, Y., Constitutive androstane receptor transcriptionally activates human CYP1A1 and CYP1A2 genes through a common regulatory element in the 5′-flanking region. Biochem. Pharmacol. 79 (2010), 261–269, 10.1016/j.bcp.2009.08.008.
71. [71] Zhou, J., Zhai, Y., Mu, Y., Gong, H., Uppal, H., Toma, D., et al. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J. Biol. Chem. 281 (2006), 15,013–15,020, 10.1074/jbc.M511116200.