The role of FXR in disorders of bile acid homeostasis

Physiology

Volumn 23, Issue 5, 2008, Pages 286-295

  Eloranta, Jyrki J ^a   Kullak Ublick, Gerd A ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; CELL RECEPTOR; DNA BINDING PROTEIN; FARNESOID X RECEPTOR; FARNESOID X-ACTIVATED RECEPTOR; LIGAND; TRANSCRIPTION FACTOR;

ANIMAL; BILIARY TRACT DISEASE; DRUG EFFECT; GENETICS; HOMEOSTASIS; HUMAN; INTESTINE; LIVER DISEASE; METABOLISM; MICROBIOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; BILE ACIDS AND SALTS; BILIARY TRACT DISEASES; DNA-BINDING PROTEINS; HOMEOSTASIS; HUMANS; INTESTINES; LIGANDS; LIVER DISEASES; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TRANSCRIPTION FACTORS;

EID: 57049149657     PISSN: 15489213     EISSN: 15489221     Source Type: Journal    
DOI: 10.1152/physiol.00020.2008     Document Type: Review

References (112)

1. Alvarez L, Jara P, Sanchez-Sabate E, Hierro L, Larrauri J, Diaz MC, Camarena C, De la Vega A, Frauca E, Lopez-Collazo E, Lapunzina P. Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1. Hum Mol Genet 13: 2451-2460, 2004.
2. Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 276: 28857-28865, 2001.
3. Anisfeld AM, Kast-Woelbern HR, Meyer ME, Jones SA, Zhang Y, Williams KJ, Willson T, Edwards PA. Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor. J Biol Chem 278: 20420-20428, 2003.
4. Barbier O, Torra IP, Sirvent A, Claudel T, Blanquart C, Duran-Sandoval D, Kuipers F, Kosykh V, Fruchart JC, Staels B. FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Gastroenterology 124: 1926-1940, 2003.
5. Berg RD. Bacterial translocation from the gastrointestinal tract. Trends Microbiol 3: 149-154, 1995.
6. Bertolotti M, Gabbi C, Anzivino C, Mitro N, Godio C, De Fabiani E, Crestani M, Del Puppo M, Ricchi M, Carulli L, Rossi A, Loria P, Carulli N. Decreased hepatic expression of PPAR-gamma coactivator-1 in cholesterol cholelithiasis. Eur J Clin Invest 36: 170-175, 2006.
7. Biddinger SB, Haas JT, Yu BB, Bezy O, Jing E, Zhang W, Unterman TG, Carey MC, Kahn CR. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 14: 778-782, 2008.
8. Boyer JL, Trauner M, Mennone A, Soroka CJ, Cai SY, Moustafa T, Zollner G, Lee JY, Ballatori N. Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol 290: G1124-G1130, 2006.
9. Carter BA, Taylor OA, Prendergast DR, Zimmerman TL, Von Furstenberg R, Moore DD, Karpen SJ. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. Pediatr Res 62: 301-306, 2007.
10. Chen F, Ananthanarayanan M, Emre S, Neimark E, Bull LN, Knisely AS, Strautnieks SS, Thompson RJ, Magid MS, Gordon R, Balasubramanian N, Suchy FJ, Shneider BL. Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity. Gastroenterology 126: 756-764, 2004.
11. Claudel T, Inoue Y, Barbier O, Duran-Sandoval D, Kosykh V, Fruchart J, Fruchart JC, Gonzalez FJ, Staels B. Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology 125: 544-555, 2003.
12. Claudel T, Staels B, Kuipers F. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 25: 2020-2030, 2005.
13. Claudel T, Sturm E, Duez H, Torra IP, Sirvent A, Kosykh V, Fruchart JC, Dallongeville J, Hum DW, Kuipers F, Staels B. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J Clin Invest 109: 961-971, 2002.
14. Cui J, Heard TS, Yu J, Lo JL, Huang L, Li Y, Schaeffer JM, Wright SD. The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X receptor confer the receptor with high sensitivity to chenodeoxycholate. J Biol Chem 277: 25963-25969, 2002.
15. Deng R, Yang D, Yang J, Yan B. Oxysterol 22(R)-hydroxycholesterol induces the expression of the bile salt export pump through nuclear receptor farsenoid X receptor but not liver X receptor. J Pharmacol Exp Ther 317: 317-325, 2006.
16. Denson LA, Sturm E, Echevarria W, Zimmerman TL, Makishima M, Mangelsdorf DJ, Karpen SJ. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 121: 140-147, 2001.
17. Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E, Weaver J, Nelson-Piercy C, de Swiet M, Warnes G, Elias E, Higgins CF, Johnston DG, McCarthy MI, Williamson C. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking. Hum Mol Genet 9: 1209-1217, 2000.
18. Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell 11: 1079-1092, 2003.
19. Eloranta JJ, Jung D, Kullak-Ublick GA. The human Na+-taurocholate cotransporting polypeptide gene is activated by glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and suppressed by bile acids via a small heterodimer partner-dependent mechanism. Mol Endocrinol 20: 65-79, 2006.
20. Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 433: 397-412, 2005.
21. Farhana L, Dawson MI, Leid M, Wang L, Moore DD, Liu G, Xia Z, Fontana JA. Adamantyl-substituted retinoid-related molecules bind small heterodimer partner and modulate the Sin3A repressor. Cancer Res 67: 318-325, 2007.
22. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, Lammert F, Stieger B, Meier PJ, Zatloukal K, Denk H, Trauner M. Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology 121: 170-183, 2001.
23. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Weiglein AH, Lammert F, Marschall HU, Tsybrovskyy O, Zatloukal K, Denk H, Trauner M. Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles. Gastroenterology 123: 1238-1251, 2002.
24. Fiorucci S, Antonelli E, Rizzo G, Renga B, Mencarelli A, Riccardi L, Orlandi S, Pellicciari R, Morelli A. The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis. Gastroenterology 127: 1497-1512, 2004.
25. Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81: 687-693, 1995.
26. Frankenberg T, Miloh T, Chen FY, Ananthanarayanan M, Sun AQ, Balasubramaniyan N, Arias I, Setchell KD, Suchy FJ, Shneider BL. The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor. Hepatology. In press.
27. +/bile acid cotransporter in extrahepatic cholestasis. Gastroenterology 110: 199-209, 1996.
28. Germain P, Staels B, Dacquet C, Spedding M, Laudet V. Overview of nomenclature of nuclear receptors. Pharmacol Rev 58: 685-704, 2006.
29. Gronemeyer H, Gustafsson JA, Laudet V. Principles for modulation of the nuclear receptor superfamily. Nat Rev Drug Discov 3: 950-964, 2004.
30. Gupta S, Stravitz RT, Dent P, Hylemon PB. Down-regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression by bile acids in primary rat hepatocytes is mediated by the c-Jun N-terminal kinase pathway. J Biol Chem 276: 15816-15822, 2001.
31. Hagenbuch B, Meier PJ. Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pflügers Arch 447: 653-665, 2004.
32. Hofmann AF. Pathogenesis of cholesterol gallstones. J Clin Gastroenterol 10, Suppl 2: S1-S11, 1988.
33. Holt JA, Luo G, Billin AN, Bisi J, McNeill YY, Kozarsky KF, Donahee M, Wang DY, Mansfield TA, Kliewer SA, Goodwin B, Jones SA. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev 17: 1581-1591, 2003.
34. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 4: 269-273, 2003.
35. Huang L, Zhao A, Lew JL, Zhang T, Hrywna Y, Thompson JR, de Pedro N, Royo I, Blevins RA, Pelaez F, Wright SD, Cui J. Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J Biol Chem 278: 51085-51090, 2003.
36. Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J, Liu J, Dong B, Huang X, Moore DD. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 312: 233-236, 2006.
37. Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, Gunyuzlu PL, Haws TF, Kassam A, Powell F, Hollis GF, Young PR, Mukherjee R, Burn TC. Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters. Gene 290: 35-43, 2002.
38. Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG, Luo G, Jones SA, Goodwin B, Richardson JA, Gerard RD, Repa JJ, Mangelsdorf DJ, Kliewer SA. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab 2: 217-225, 2005.
39. Inagaki T, Moschetta A, Lee YK, Peng L, Zhao G, Downes M, Yu RT, Shelton JM, Richardson JA, Repa JJ, Mangelsdorf DJ, Kliewer SA. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci USA 103: 3920-3925, 2006.
40. Ismair MG, Stieger B, Cattori V, Hagenbuch B, Fried M, Meier PJ, Kullak-Ublick GA. Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver. Gastroenterology 121: 1185-1190, 2001.
41. Jansen PL, Sturm E. Genetic cholestasis, causes and consequences for hepatobiliary transport. Liver Int 23: 315-322, 2003.
42. Johansson L, Bavner A, Thomsen JS, Farnegardh M, Gustafsson JA, Treuter E. The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated estrogen receptors. Mol Cell Biol 20: 1124-1133, 2000.
43. Jung D, Hagenbuch B, Gresh L, Pontoglio M, Meier PJ, Kullak-Ublick GA. Characterization of the human OATP-C (SLC21A6) gene promoter and regulation of liver-specific OATP genes by hepatocyte nuclear factor 1 alpha. J Biol Chem 276: 37206-37214, 2001.
44. Jung D, Kullak-Ublick GA. Hepatocyte nuclear factor 1 alpha: a key mediator of the effect of bile acids on gene expression. Hepatology 37: 622-631, 2003.
45. Jung D, Podvinec M, Meyer UA, Mangelsdorf DJ, Fried M, Meier PJ, Kullak-Ublick GA. Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology 122: 1954-1966, 2002.
46. Kanaya E, Shiraki T, Jingami H. The nuclear bile acid receptor FXR is activated by PGC-1alpha in a ligand-dependent manner. Biochem J 382: 913-921, 2004.
47. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 277: 2908-2915, 2002.
48. Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M. A G protein-coupled receptor responsive to bile acids. J Biol Chem 278: 9435-9440, 2003.
49. Keitel V, Vogt C, Haussinger D, Kubitz R. Combined mutations of canalicular transporter proteins cause severe intrahepatic cholestasis of pregnancy. Gastroenterology 131: 624-629, 2006.
50. Kemper JK, Kim H, Miao J, Bhalla S, Bae Y. Role of an mSin3A-Swi/Snf chromatin remodeling complex in the feedback repression of bile acid biosynthesis by SHP. Mol Cell Biol 24: 7707-7719, 2004.
51. Kerr TA, Saeki S, Schneider M, Schaefer K, Berdy S, Redder T, Shan B, Russell DW, Schwarz M. Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis. Dev Cell 2: 713-720, 2002.
52. Kim I, Morimura K, Shah Y, Yang Q, Ward JM, Gonzalez FJ. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 28: 940-946, 2007.
53. Konig J, Nies AT, Cui Y, Leier I, Keppler D. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim Biophys Acta 1461: 377-394, 1999.
54. Kovacs P, Kress R, Rocha J, Kurtz U, Miquel JF, Nervi F, Mendez-Sanchez N, Uribe M, Bock HH, Schirin-Sokhan R, Stumvoll M, Mossner J, Lammert F, Wittenburg H. Variation of the gene encoding the nuclear bile salt receptor FXR and gallstone susceptibility in mice and humans. J Hepatol 48: 116-124, 2008.
55. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B. Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 120: 525-533, 2001.
56. Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126: 322-342, 2004.
57. Laffitte BA, Kast HR, Nguyen CM, Zavacki AM, Moore DD, Edwards PA. Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J Biol Chem 275: 10638-10647, 2000.
58. Landrier JF, Eloranta JJ, Vavricka SR, Kullak-Ublick GA. The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes. Am J Physiol Gastrointest Liver Physiol 290: G476-G485, 2006.
59. Lee H, Zhang Y, Lee FY, Nelson SF, Gonzalez FJ, Edwards PA. FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine. J Lipid Res 47: 201-214, 2006
60. Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD. The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression. Mol Cell Biol 20: 187-195, 2000.
61. Lee YK, Moore DD. Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner. J Biol Chem 277: 2463-2467, 2002.
62. Lew JL, Zhao A, Yu J, Huang L, De Pedro N, Pelaez F, Wright SD, Cui J. The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion. J Biol Chem 279: 8856-8861, 2004.
63. Li T, Jahan A, Chiang JY. Bile acids and cytokines inhibit the human cholesterol 7 alpha-hydroxylase gene via the JNK/c-jun pathway in human liver cells. Hepatology 43: 1202-1210, 2006.
64. Liu Y, Binz J, Numerick MJ, Dennis S, Luo G, Desai B, MacKenzie KI, Mansfield TA, Kliewer SA, Goodwin B, Jones SA. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J Clin Invest 112: 1678-1687, 2003.
65. Lorenzo-Zuniga V, Bartoli R, Planas R, Hofmann AF, Vinado B, Hagey LR, Hernandez JM, Mane J, Alvarez MA, Ausina V, Gassull MA. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology 37: 551-557, 2003.
66. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B. Identification of a nuclear receptor for bile acids. Science 284: 1362-1365, 1999.
67. Maloney PR, Parks DJ, Haffner CD, Fivush AM, Chandra G, Plunket KD, Creech KL, Moore LB, Wilson JG, Lewis MC, Jones SA, Willson TM. Identification of a chemical tool for the orphan nuclear receptor FXR. J Med Chem 43: 2971-2974, 2000.
68. Marzolini C, Tirona RG, Gervasini G, Poonkuzhali B, Assem M, Lee W, Leake BF, Schuetz JD, Schuetz EG, Kim RB. A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Mol Endocrinol 21: 1769-1780, 2007.
69. Meier Y, Zodan T, Lang C, Zimmermann R, Kullak-Ublick GA, Meier PJ, Stieger B, Pauli-Magnus C. Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World J Gastroenterol 14: 38-45, 2008.
70. Meirhaeghe A, Amouyel P. Impact of genetic variation of PPARgamma in humans. Mol Genet Metab 83: 93-102, 2004.
71. Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med 10: 1352-1358, 2004.
72. Mullenbach R, Bennett A, Tetlow N, Patel N, Hamilton G, Cheng F, Chambers J, Howard R, Taylor-Robinson SD, Williamson C. ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy. Gut 54: 829-834, 2005.
73. Nagano M, Kuroki S, Mizuta A, Furukawa M, Noshiro M, Chijiiwa K, Tanaka M. Regulation of bile acid synthesis under reconstructed enterohepatic circulation in rats. Steroids 69: 701-709, 2004.
74. Nathan C. Inducible nitric oxide synthase: what difference does it make? J Clin Invest 100: 2417-2423, 1997.
75. Neimark E, Chen F, Li X, Shneider BL. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology 40: 149-156, 2004.
76. Otte K, Kranz H, Kober I, Thompson P, Hoefer M, Haubold B, Remmel B, Voss H, Kaiser C, Albers M, Cheruvallath Z, Jackson D, Casari G, Koegl M, Paabo S, Mous J, Kremoser C, Deuschle U. Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Mol Cell Biol 23: 864-872, 2003.
77. Painter JN, Savander M, Ropponen A, Nupponen N, Riikonen S, Ylikorkala O, Lehesjoki AE, Aittomaki K. Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of pregnancy. Eur J Hum Genet 13: 435-439, 2005.
78. Pandak WM, Li YC, Chiang JY, Studer EJ, Gurley EC, Heuman DM, Vlahcevic ZR, Hylemon PB. Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat. J Biol Chem 266: 3416-3421, 1991.
79. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM. Bile acids: natural ligands for an orphan nuclear receptor. Science 284: 1365-1368, 1999.
80. Pauli-Magnus C, Lang T, Meier Y, Zodan-Marin T, Jung D, Breymann C, Zimmermann R, Kenngott S, Beuers U, Reichel C, Kerb R, Penger A, Meier PJ, Kullak-Ublick GA. Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pharmacogenetics 14: 91-102, 2004.
81. Plass JR, Mol O, Heegsma J, Geuken M, Faber KN, Jansen PL, Muller M. Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump. Hepatology 35: 589-596, 2002.
82. Rao A, Haywood J, Craddock AL, Belinsky MG, Kruh GD, Dawson PA. The organic solute transporter alpha-beta, Ostalpha-Ostbeta, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci USA 105: 3891-3896, 2008.
83. Renner O, Harsch S, Strohmeyer A, Schimmel S, Stange EF. Reduced ileal expression of organic solute transporter alpha and beta (OSTalpha - OSTbeta) in non-obese gallstone disease. J Lipid Res 29: 2045-2054, 2008.
84. Ricketts ML, Boekschoten MV, Kreeft AJ, Hooiveld GJ, Moen CJ, Muller M, Frants RR, Kasanmoentalib S, Post SM, Princen HM, Porter JG, Katan MB, Hofker MH, Moore DD. The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors. Mol Endocrinol 21: 1603-1616, 2007.
85. Sato H, Macchiarulo A, Thomas C, Gioiello A, Une M, Hofmann AF, Saladin R, Schoonjans K, Pellicciari R, Auwerx J. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies. J Med Chem 51: 1831-1841, 2008.
86. Schneider G, Paus TC, Kullak-Ublick GA, Meier PJ, Wienker TF, Lang T, van de Vondel P, Sauerbruch T, Reichel C. Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and intrahepatic cholestasis of pregnancy. Hepatology 45: 150-158, 2007.
87. Schuetz EG, Strom S, Yasuda K, Lecureur V, Assem M, Brimer C, Lamba J, Kim RB, Ramachandran V, Komoroski BJ, Venkataramanan R, Cai H, Sinal CJ, Gonzalez FJ, Schuetz JD. Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J Biol Chem 276: 39411-39418, 2001.
88. Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science 272: 1336-1339, 1996.
89. Smith CL, O'Malley BW. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev 25: 45-71, 2004.
90. Stieger B, Meier Y, Meier PJ. The bile salt export pump. Pflügers Arch 453: 611-620, 2007.
91. Tai ES, Demissie S, Cupples LA, Corella D, Wilson PW, Schaefer EJ, Ordovas JM. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 22: 805-810, 2002.
92. Thelle DS. Coffee, tea and coronary heart disease. Curr Opin Lipidol 6: 25-27, 1995.
93. Tverdal A, Stensvold I, Solvoll K, Foss OP, Lund-Larsen P, Bjartveit K. Coffee consumption and death from coronary heart disease in middle aged Norwegian men and women. BMJ 300: 566-569, 1990.
94. Ujhazy P, Ortiz D, Misra S, Li S, Moseley J, Jones H, Arias IM. Familial intrahepatic cholestasis 1: studies of localization and function. Hepatology 34: 768-775, 2001.
95. Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 371: 1-12, 2006.
96. van Mil SW, Klomp LW, Bull LN, Houwen RH. FIC1 disease: a spectrum of intrahepatic cholestatic disorders. Semin Liver Dis 21: 535-544, 2001.
97. Van Mil SW, Milona A, Dixon PH, Mullenbach R, Geenes VL, Chambers J, Shevchuk V, Moore GE, Lammert F, Glantz AG, Mattsson LA, Whittaker J, Parker MG, White R, Williamson C. Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. Gastroenterology 133: 507-516, 2007.
98. Wallace JL, Miller MJ. Nitric oxide in mucosal defense: a little goes a long way. Gastroenterology 119: 512-520, 2000.
99. Wang H, Chen J, Hollister K, Sowers LC, Forman BM. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 3: 543-553, 1999.
100. Wang L, Lee YK, Bundman D, Han Y, Thevananther S, Kim CS, Chua SS, Wei P, Heyman RA, Karin M, Moore DD. Redundant pathways for negative feedback regulation of bile acid production. Dev Cell 2: 721-731, 2002.
101. Wang S, Lai K, Moy FJ, Bhat A, Hartman HB, Evans MJ. The nuclear hormone receptor farnesoid X receptor (FXR) is activated by androsterone. Endocrinology 147: 4025-4033, 2006.
102. Weusten-Van der Wouw MP, Katan MB, Viani R, Huggett AC, Liardon R, Liardon R, Lund-Larsen PG, Thelle DS, Ahola I, Aro A, et al. Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes. J Lipid Res 35: 721-733, 1994.
103. Wittenburg H, Lyons MA, Li R, Churchill GA, Carey MC, Paigen B. FXR and ABCG5/ABCG8 as determinants of cholesterol gallstone formation from quantitative trait locus mapping in mice. Gastroenterology 125: 868-881, 2003.
104. Wolters H, Elzinga BM, Baller JF, Boverhof R, Schwarz M, Stieger B, Verkade HJ, Kuipers F. Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice. J Hepatol 37: 556-563, 2002.
105. Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 384: 458-460, 1996.
106. Yang F, Huang X, Yi T, Yen Y, Moore DD, Huang W. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res 67: 863-867, 2007.
107. Zavacki AM, Lehmann JM, Seol W, Willson TM, Kliewer SA, Moore DD. Activation of the orphan receptor RIP14 by retinoids. Proc Natl Acad Sci USA 94: 7909-7914, 1997.
108. Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev 18: 157-169, 2004.
109. Zhang Y, Kast-Woelbern HR, Edwards PA. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem 278: 104-110, 2003.
110. Zollner G, Fickert P, Fuchsbichler A, Silbert D, Wagner M, Arbeiter S, Gonzalez FJ, Marschall HU, Zatloukal K, Denk H, Trauner M. Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine. J Hepatol 39: 480-488, 2003.
111. Zollner G, Fickert P, Silbert D, Fuchsbichler A, Marschall HU, Zatloukal K, Denk H, Trauner M. Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis. J Hepatol 38: 717-727, 2003.
112. Zollner G, Fickert P, Zenz R, Fuchsbichler A, Stumptner C, Kenner L, Ferenci P, Stauber RE, Krejs GJ, Denk H, Zatloukal K, Trauner M. Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases. Hepatology 33: 633-646, 2001.