Bile acids and their signaling pathways: Eclectic regulators of diverse cellular functions

Cellular and Molecular Life Sciences

Volumn 64, Issue 19-20, 2007, Pages 2477-2491

  Scotti, E ^a   Gilardi, F ^a   Godio, C ^a   Gers, E ^a   Krneta, J ^a   Mitro, N ^a,b   De Fabiani, E ^a   Caruso, D ^a   Crestani, M ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Energy expenditure; Enterohepatic circulation; Glucose metabolism; Lipid metabolism; Liver regeneration; Nuclear receptors

Indexed keywords

BILE ACID; FARNESOID X RECEPTOR; FARNESOL; G PROTEIN COUPLED RECEPTOR; GLUCOSE; LIPID;

BILE ACID METABOLISM; BILE ACID SYNTHESIS; CELL FUNCTION; CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; ENERGY EXPENDITURE; GLUCOSE METABOLISM; HUMAN; LIPID METABOLISM; LIVER CIRCULATION; LIVER REGENERATION; REVIEW; SCIENTIST;

BILE ACIDS AND SALTS; DNA-BINDING PROTEINS; GLUCOSE; HUMANS; LIPID METABOLISM; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 35648938666     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-007-7280-y     Document Type: Review

References (124)

1. Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlmann, T., Noonan, D. J., Burka, L. T., McMorris, T., Lamph, W. W. et al. (1995) Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81, 687-693.
2. Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J. and Shan, B. (1999) Identification of a nuclear receptor for bile acids. Science 284, 1362-1365.
3. Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., Moore, D. D. et al. (1999) Bile acids: natural ligands for an orphan nuclear receptor. Science 284, 1365-1368.
4. Wang, H., Chen, J., Hollister, K., Sowers, L. C. and Forman, B. M. (1999) Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell 3, 543-553.
5. Zhang, Y., Kast-Woelbern, H. R. and Edwards, P. A. (2003) Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J. Biol. Chem. 278, 104-110.
6. Kanda, T., Foucand, L., Nakamura, Y., Niot, I., Besnard, P., Fujita, M., Sakai, Y., Hatakeyama, K., Ono, T. and Fujii, H. (1998) Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells. Biochem. J. 330, 261-265.
7. Chiang, J. Y. L., Kimmel, R., Weinberger, C. and Stroup, D. (2000) Farnesoid X receptor responds to bile acids and represses cholesterol 7α-hydroxylase gene (CYP7A1) Transcription. J. Biol. Chem. 275, 10918-10924.
8. Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G. and Gonzalez, F. J. (2000) Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102, 731-744.
9. Lu, T. T., Makishima, M., Repa, J. J., Schoonjans, K., Kerr, T. A., Auwerx, J. and Mangelsdorf, D. J. (2000) Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell 6, 507-515.
10. Goodwin, B., Jones, S. A., Price, R. R., Watson, M. A., McKee, D. D., Moore, L. B., Galardi, C., Wilson, J. G., Lewis, M. C., Roth, M. E. et al. (2000) A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell 6, 517-26.
11. Lee, Y.-K., Dell, H., Dowhan, D. H., Hadzopoulou-Cladaras, M. and Moore, D. D. (2000)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.
12. Kerr, T., Saeki, S., Schneider, M., Schaefer, K., Berdy, S., Redder, T., Shan, B., Russell, D. and Schwarz, M. (2002) Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis. Dev. Cell 2, 713-720.
13. Wang, L., Lee, Y., Bundman, D., Han, Y., Thevananther, S., Kim, C., Chua, S., Wei, P., Heyman, R., Karin, M. et al. (2002) Redundant pathways for negative feedback regulation of bile acid production. Dev. Cell 2, 721-731.
14. Gupta, S., Stravitz, R. T., Dent, P. and Hylemon, P. B. (2001) Down-regulation of cholesterol 7α-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.
15. Ito, S., Fujimori, T., Furuya, A., Satoh, J., Nabeshima, Y. and Nabeshima, Y.-i. (2005) Impaired negative feedback suppression of bile acid synthesis in mice lacking bKlotho. J. Clin. Invest. 115, 2202-2208.
16. Holt, J. A., Luo, G., Billin, A. N., Bisi, J., McNeill, Y. Y., Kozarsky, K. F., Donahee, M., Wang, D. Y., Mansfield, T. A., Kliewer, S. A. et al. (2003) Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 17, 1581-1591.
17. Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A. et al. (2005) Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2, 217-225.
18. Pandak, W. M., Heuman, D. M., Hylemon, P. B., Chiang, J. Y. L. and Vlahcevic, Z. R. (1995) Failure of intravenous infusion of taurocholate to down-regulate cholesterol 7α-hydroxylase in rats with biliary fistulas. Gastroenterology 108, 533-544.
19. De Fabiani, E., Mitro, N., Anzulovich, A. C., Pinelli, A., Galli, G. and Crestani, M. (2001) The negative effects of bile acids and tumor necrosis factor-α on the transcription of cholesterol 7α-hydroxylase gene (CYP7A1) converge to hepatocyte nuclear factor-4. A novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors. J. Biol. Chem. 276, 30708-30716.
20. De Fabiani, E., Mitro, N., Gilardi, F., Caruso, D., Galli, G. and Crestani, M. (2003) Coordinated control of cholesterol catabolism to bile acids and of gluconeogenesis via a novel mechanism of transcription regulation linked to the fasted-to-fed cycle. J. Biol. Chem. 278, 39124-39132.
21. Kemper, J. K., Kim, H., Miao, J., Bhalla, S. and Bae, Y. (2004) 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.
22. Boulias, K. and Talianidis, I. (2004) Functional role of G9a-induced histone methylation in small heterodimer partner-mediated transcriptional repression. Nucl. Acids Res. 32, 6096-6103.
23. Urizar, N. L., Liverman, A. B., Dodds, D. N. T., Silva, F. V., Ordentlich, P., Yan, Y., Gonzalez, F. J., Heyman, R. A., Mangelsdorf, D. J. and Moore, D. D. (2002) A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296, 1703-1706.
24. Wu, J., Xia, C., Meier, J., Li, S., Hu, X. and Lala, D. S. (2002) The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol. Endocrinol. 16, 1590-1597.
25. Owsley, E. and Chiang, J. Y. L. (2003) Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7α-hydroxylase gene. Biochem. Biophys. Res. Commun. 304, 191-195.
26. Staudinger, J. L., Goodwin, B., Jones, S. A., Hawkins-Brown, D., MacKenzie, K. I., LaTour, A., Liu, Y., Klaassen, C. D., Brown, K. K., Reinhard, J. et al. (2001) The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. USA 98, 3369-3374.
27. Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C. M., Nelson, M. C., Ong, E. S., Waxman, D. J. and Evans, R. M. (2001) An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Natl. Acad. Sci. USA 98, 3375-3380.
28. Goodwin, B., Gauthier, K. C., Umetani, M., Watson, M. A., Lochansky, M. I., Collins, J. L., Leitersdorf, E., Mangelsdorf, D. J., Kliewer, S. A. and Repa, J. J. (2003) Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc. Natl. Acad. Sci. USA 100, 223-228.
29. Bhalla, S., Ozalp, C., Fang, S., Xiang, L. and Kemper, J. K. (2004) Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1a: functional implications in hepatic cholesterol and glucose metabolism. J. Biol. Chem. 279, 45139-45147.
30. Li, T. and Chiang, J. Y. L. (2005) Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7a-hydroxylase gene transcription. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G74-G84.
31. Barbier, O., Torra, I. P., Sirvent, A., Claudel, T., Blanquart, C., Duran-Sandoval, D., Kuipers, F., Kosykh, V., Fruchart, J. C. and Staels, B. (2003) FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Gastroenterology 124, 1926-1940.
32. Trottier, J., Verreault, M., Grepper, S., Monté, D., Bélanger, J., Kaeding, J., Caron, P., Inaba, T. T. and Barbier, O. (2006) Human UDP-glucuronosyltransferase (UGT)1A3 enzyme conjugates chenodeoxycholic acid in the liver. Hepatology 44, 1158-1170.
33. Strautnieks, S. S., Bull, L. N., Knisely, A. S., Kocoshis, S. A., Dahl, N., Arnell, H., Sokal, E., Dahan, K., Childs, S., Ling, V. et al. (1998) A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat. Genet. 20, 233.
34. Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J. and Suchy, F. J. (2001) Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J. Biol. Chem. 276, 28857-28865.
35. Schuetz, E. G., Strom, S., Yasuda, K., Lecureur, V., Assem, M., Brimer, C., Lamba, J., Kim, R. B., Ramachandran, V., Komoroski, B. J. et al. (2001) Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J. Biol. Chem. 276, 39411-39418.
36. Plass, J., Mol, O., Heegsma, J., Geuken, M., Faber, K. N., Jansen, P. L. M. and Müller, M. (2002) 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.
37. van Helvoort, A., Smith, A. J., Sprong, H., Fritzsche, I., Schinkel, A. H., Borst, P. and van Meer, G. (1996) MDR1 Pglycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87, 507-517.
38. Huang, L., Zhao, A., Lew, J.-L., Zhang, T., Hrywna, Y., Thompson, J. R., de Pedro, N., Royo, I., Blevins, R. A., Pelaez, F. et al. (2003) Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J. Biol. Chem. 278, 51085-51090.
39. de Vree, J. M. L., Jacquemin, E., Sturm, E., Cresteil, D., Bosma, P. J., Aten, J., Deleuze, J.-F., Desrochers, M., Burdelski, M., Bernard, O. et al. (1998) Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc. Natl. Acad. Sci. USA 95, 282-287.
40. Moschetta, A., Bookout, A. and Mangelsdorf, D. (2004) Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat. Med. 10, 1352-1358.
41. Fickert, P., Zollner, G., Fuchsbichler, A., Stumptner, C., Pojer, C., Zenz, R., Lammert, F., Stieger, B., Meier, P. J., Zatloukal, K. et al. (2001) Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology 121, 170-183.
42. +-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation. J. Hepatol. 27, 1051-1056.
43. +/bile acid cotransporter in extrahepatic cholestasis. Gastroenterology 110, 199-209.
44. Denson, L. A., Sturm, E., Echevarria, W., Zimmerman, T. L., Makishima, M., Mangelsdorf, D. J. and Karpen, S. J. (2001) The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology 121, 140-147.
45. Li, D., Zimmerman, T. L., Thevananther, S., Lee, H.-Y., Kurie, J. M. and Karpen, S. J. (2002) Interleukin-1β-mediated suppression of RXR:RAR transactivation of the Ntcp promoter is JNK-dependent. J. Biol. Chem. 277, 31416-31422.
46. Jung, D., Hagenbuch, B., Fried, M., Meier, P. J. and Kullak-Ublick, G. A. (2004) Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G752-G761.
47. Jung, D. and Kullak-Ublick, G. A. (2003) Hepatocyte nuclear factor 1α: a key mediator of the effect of bile acids on gene expression. Hepatology 37, 622-631.
48. Jung, D., Podvinec, M., Meyer, U., Mangelsdorf, D., Fried, M., Meier, P. and Kullak-Ublick, G. (2002) Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology 122, 1954-1966.
49. Yamaguchi, H., Okada, M., Akitaya, S., Ohara, H., Mikkaichi, T., Ishikawa, H., Sato, M., Matsuura, M., Saga, T., Unno, M. et al. (2006) Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J. Lipid Res. 47, 1196-1202.
50. Wong, M. H., Oelkers, P., Craddock, A. L. and Dawson, P. A. (1994) Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter. J. Biol. Chem. 269, 1340-1347.
51. Oelkers, P., Kirby, L. C., Heubi, J. E. and Dawson, P. A. (1997) Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2 ). J. Clin. Invest. 99, 1880-1887.
52. Chen, F., Ma, L., Dawson, P. A., Sinal, C. J., Sehayek, E., Gonzalez, F. J., Breslow, J., Ananthanarayanan, M. and Shneider, B. L. (2003) Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter. J. Biol. Chem. 278, 19909-19916.
53. Neimark, E., Chen, F., Li, X. and Shneider, B. (2004) Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology 40, 149-156.
54. Jung, D., Fantin, A. C., Scheurer, U., Fried, M. and Kullak-Ublick, G. A. (2004) Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 53, 78-84.
55. Borgius, L. J., Steffensen, K. R., Gustafsson, J.-A. and Treuter, E. (2002) Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP. J. Biol. Chem. 277, 49761-49766.
56. Gong, Y. Z., Everett, E. T., Schwartz, D. A., Norris, J. S. and Wilson, F. A. (1994) Molecular cloning, tissue distribution, and expression of a 14-kDa bile acid-binding protein from rat ileal cytosol. Proc. Natl. Acad. Sci. U.S.A. 91, 4741-4745.
57. Eloranta, J. and Kullak-Ublick, G. (2005) Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch. Biochem. Biophys. 433, 397-412.
58. Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J. et al. (2006) Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl. Acad. Sci. USA 103, 3920-3925.
59. Berg, R. D. (1995) Bacterial translocation from the gastrointestinal tract. Trends Microbiol. 3, 149-154.
60. Cahill, C. J., Pain, J. A. and Bailey, M. E. (1987) Bile salts, endotoxin and renal function in obstructive jaundice. Surg. Gynecol. Obstet. 165, 519-522.
61. Hill, M. J., Drasar, B. S., Williams, R. E., Meade, T. W., Cox, A. G., Simpson, J. E. and Morson, B. C. (1975) Faecal bile-acids and clostridia in patients with cancer of the large bowel. Lancet 1, 535-539.
62. Reddy, B. S. and Wynder, E. L. (1977) Metabolic epidemiology of colon cancer: fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps. Cancer 39, 2533-2539.
63. Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M., Haussler, M. R. and Mangelsdorf, D. J. (2002) Vitamin D receptor as an intestinal bile acid sensor. Science 296, 1313-1316.
64. Kallay, E., Pietschmann, P., Toyokuni, S., Bajna, E., Hahn, P., Mazzucco, K., Bieglmayer, C., Kato, S. and Cross, H. S. (2001) Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage. Carcinogenesis 22, 1429-1435.
65. Angelin, B., Einarsson, K., Hellstrom, K. and Leijd, B. (1978) Effects of cholestyramine and chenodeoxycholic acid on the metabolism of endogenous triglyceride in hyperlipoproteinemia. J. Lipid Res. 19, 1017-1024.
66. Beil, U., Crouse, J. R., Einarsson, K. and Grundy, S. M. (1982) Effects of interruption of the enterohepatic circulation of bile acids on the transport of very low density-lipoprotein triglycerides. Metabolism 31, 438-444.
67. Crouse, J. R., 3rd (1987) Hypertriglyceridemia: a contra-indication to the use of bile acid binding resins. Am. J. Med. 83, 243-248.
68. Bateson, M. C., Maclean, D., Evans, J. R. and Bouchier, I. A. (1978) Chenodeoxycholic acid therapy for hypertriglyceridaemia in men. Br. J. Clin. Pharmacol. 5, 249-254.
69. Carulli, N., Ponz de Leon, M., Podda, M., Zuin, M., Strata, A., Frigerio, G. and Digrisolo, A. (1981) Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial. J. Clin. Pharmacol. 21, 436-442.
70. Horton, J. D., Goldstein, J. L. and Brown, M. S. (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125-1131.
71. Schoonjans, K., Staels, B. and Auwerx, J. (1996) Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J. Lipid Res. 37, 907-925.
72. Watanabe, M., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D. and Auwerx, J. (2004) Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J. Clin. Invest. 113, 1408-1418.
73. Kalaany, N. Y., Gauthier, K. C., Zavacki, A. M., Mammen, P. P., Kitazume, T., Peterson, J. A., Horton, J. D., Garry, D. J., Bianco, A. C. and Mangelsdorf, D. J. (2005) LXRs regulate the balance between fat storage and oxidation. Cell Metab. 1, 231-2344.
74. Repa, J. J., Liang, G., Ou, J., Bashmakov, Y., Lobaccaro, J. M., Shimomura, I., Shan, B., Brown, M. S., Goldstein, J. L. and Mangelsdorf, D. J. (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ. Genes Dev. 14, 2819-2830.
75. Boulias, K., Katrakili, N., Bamberg, K., Underhill, P., Greenfield, A. and Talianidis, I. (2005) Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP. EMBO J. 24, 2624-2633.
76. Matsukuma, K. E., Bennett, M. K., Huang, J., Wang, L., Gil, G. and Osborne, T. F. (2006) Coordinated control of bile acids and lipogenesis through FXR dependent regulation of fatty acid synthase. J. Lipid Res. 47, 2754-2761.
77. Evans, R. M., Barish, G. D. and Wang, Y. X. (2004) PPARs and the complex journey to obesity. Nat. Med. 10, 355-361.
78. Pineda Torra, I., Claudel, T., Duval, C., Kosykh, V., Fruchart, J.-C. and Staels, B. (2003) Bile acids induce the expression of the human peroxisome proliferator-activated receptor α gene via activation of the farnesoid X receptor. Mol. Endocrinol. 17, 259-272.
79. Savkur, R. S., Bramlett, K. S., Michael, L. F. and Burris, T. P. (2005) Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor. Biochem. Biophys. Res. Commun. 329, 391-396.
80. Hirokane, H., Nakahara, M., Tachibana, S., Shimizu, M. and Sato, R. (2004) Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. J. Biol. Chem. 279, 45685-45692.
81. Kanaya, E., Shiraki, T. and Jingami, H. (2004) The nuclear bile acid receptor FXR is activated by PGC-1a in a ligand-dependent manner. Biochem. J. 382, 913-921.
82. Savkur, R. S., Thomas, J. S., Bramlett, K. S., Gao, Y., Michael, L. F. and Burris, T. P. (2005) Ligand-dependent coactivation of the human bile acid receptor FXR by the peroxisome proliferator-activated receptor g coactivator-1a. J. Pharmacol. Exp. Ther. 312, 170-178.
83. Zhang, Y., Castellani, L. W., Sinal, C. J., Gonzalez, F. J. and Edwards, P. A. (2004) Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) regulates triglyceride metabolismby activation of the nuclear receptor FXR. Genes Dev. 18, 157-169.
84. Mak, P. A., Kast-Woelbern, H. R., Anisfeld, A. M. and Edwards, P. A. (2002) Identification of PLTP as an LXR target gene and apoE as an FXR target gene reveals overlapping targets for the two nuclear receptors. J. Lipid Res. 43, 2037-2041.
85. Carlberg, C. (1995) Mechanisms of nuclear signalling by vitamin D3: interplay with retinoid and thyroid hormone signalling. Eur. J. Biochem. 231, 517-524.
86. Goudriaan, J. R., Espirito Santo, S. M., Voshol, P. J., Teusink, B., van Dijk, K. W., van Vlijmen, B. J., Romijn, J. A., Havekes, L. M. and Rensen, P. C. (2004) The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis. J. Lipid Res. 45, 1475-1481.
87. Sirvent, A., Claudel, T., Martin, G., Brozek, J., Kosykh, V., Darteil, R., Hum, D. W., Fruchart, J. C. and Staels, B. (2004) The farnesoid X receptor induces very low density lipoprotein receptor gene expression. FEBS Lett. 566, 173-177.
88. Anisfeld, A. M., Kast-Woelbern, H. R., Meyer, M. E., Jones, S. A., Zhang, Y., Williams, K. J., Willson, T. and Edwards, P. A. (2003) Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor. J. Biol. Chem. 278, 20420-20428.
89. Urizar, N. L., Dowhan, D. H. and Moore, D. D. (2000) The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. J. Biol. Chem. 275, 39313-39317.
90. Sirvent, A., Verhoeven, A. J., Jansen, H., Kosykh, V., Darteil, R. J., Hum, D. W., Fruchart, J. C. and Staels, B. (2004) Farnesoid X receptor represses hepatic lipase gene expression. J. Lipid Res. 45, 2110-2115.
91. Claudel, T., Sturm, E., Duez, H., Torra, I. P., Sirvent, A., Kosykh, V., Fruchart, J.-C., Dallongeville, J., Hum, D. W., Kuipers, F. et al. (2002) Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J. Clin. Invest. 109, 961-971.
92. Srivastava, R. A., Srivastava, N. and Averna, M. (2000) Dietary cholic acid lowers plasma levels of mouse and human apolipoprotein A-I primarily via a transcriptional mechanism. Eur. J. Biochem. 267, 4272-4280.
93. Kast, H. R., Nguyen, C. M., Sinal, C. J., Jones, S. A., Laffitte, B. A., Reue, K., Gonzalez, F. J., Willson, T. M. and Edwards, P. A. (2001) Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids. Mol. Endocrinol. 15, 1720-1728.
94. Claudel, T., Inoue, Y., Barbier, O., Duran-Sandoval, D., Kosykh, V., Fruchart, J., Fruchart, J., Gonzalez, F. and Staels, B. (2003) Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology 125, 544-555.
95. Cianflone, K., Xia, Z. and Chen, L. Y. (2003) Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim. Biophys. Acta 1609, 127-143.
96. Li, J., Pircher, P. C., Schulman, I. G. and Westin, S. K. (2005) Regulation of complement C3 expression by the bile acid receptor FXR. J. Biol. Chem. 280, 7427-7434.
97. Rizzo, G., Disante, M., Mencarelli, A., Renga, B., Gioiello, A., Pellicciari, R. and Fiorucci, S. (2006) The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo. Mol. Pharmacol. 70, 1164-1173.
98. Cariou, B., van Harmelen, K., Duran-Sandoval, D., van Dijk, T. H., Grefhorst, A., Abdelkarim, M., Caron, S., Torpier, G., Fruchart, J.-C., Gonzalez, F. J. et al. (2006) The Farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J. Biol. Chem. 281, 11039-11049.
99. Duran-Sandoval, D., Cariou, B., Percevault, F., Hennuyer, N., Grefhorst, A., van Dijk, T. H., Gonzalez, F. J., Fruchart, J.-C., Kuipers, F. and Staels, B. (2005) The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition. J. Biol. Chem. 280, 29971-29979.
100. Duran-Sandoval, D., Mautino, G., Martin, G., Percevault, F., Barbier, O., Fruchart, J. C., Kuipers, F. and Staels, B. (2004) Glucose regulates the expression of the farnesoid X receptor in liver. Diabetes 53, 890-898.
101. Stayrook, K. R., Bramlett, K. S., Savkur, R. S., Ficorilli, J., Cook, T., Christe, M. E., Michael, L. F. and Burris, T. P. (2005) Regulation of carbohydrate metabolism by the farnesoid X receptor. Endocrinology 146, 984-991.
102. Yamagata, K., Daitoku, H., Shimamoto, Y., Matsuzaki, H., Hirota, K., Ishida, J. and Fukamizu, A. (2004) Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1. J. Biol. Chem. 279, 23158-23165.
103. Ma, K., Saha, P. K., Chan, L. and Moore, D. D. (2006) Farnesoid X receptor is essential for normal glucose homeostasis. J. Clin. Invest. 116, 1102-1109.
104. Finck, B. N., Bernal-Mizrachi, C., Han, D. H., Coleman, T., Sambandam, N., LaRiviere, L. L., Holloszy, J. O., Semenkovich, C. F. et al. (2005) A potential link between muscle peroxisome proliferator-activated receptor-a signaling and obesity-related diabetes. Cell Metab. 1, 133-144.
105. Zhang, Y., Lee, F. Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F. J., Willson, T. M. and Edwards, P. A. (2006) Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc. Natl. Acad. Sci. USA 103, 1006-1011.
106. Girard, J., Ferre, P. and Foufelle, F. (1997) Mechanisms by which carbohydrates regulate expression of genes for glycolytic and lipogenic enzymes. Annu. Rev. Nutr. 17, 325-352.
107. Han, S., Studer, E., Gupta, S., Fang, Y., Qiao, L., Li, W., Grant, S., Hylemon, P. and Dent, P. (2004) Bile acids enhance the activity of the insulin receptor and glycogen synthase in primary rodent hepatocytes. Hepatology 39, 456-63.
108. Dueland, S., France, D., Wang, S.-L., Trawick, J. D. and Davis, R. A. (1997) Cholesterol 7α-hydroxylase influences the expression of hepatic apoA-I in two inbred mouse strains displaying different susceptabilities to atherosclerosis and in hepatoma cells. J. Lipid Res. 38, 1445-1453.
109. Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y. et al. (2003) AG protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278, 9435-9440.
110. Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama E., Itadani, H. and Tanaka, K. (2002) Identification of membrane-type receptor for bile acids (MBAR). Biochem. Biophys. Res. Commun. 298, 714-719.
111. Katsuma, S., Hirasawa, A. and Tsujimoto, G. (2005) Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem. Biophys. Res. Commun. 329, 386-390.
112. Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T. et al. (2006) Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439, 484.
113. Maruyama, T., Tanaka, K., Suzuki, J., Miyoshi, H., Harada, N., Nakamura, T., Miyamoto, Y., Kanatani, A. and Tamai, Y. (2006) Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J. Endocrinol. 191, 197-205.
114. Huang, W., Ma, K., Zhang, J., Qatanani, M., Cuvillier, J., Liu, J., Dong, B., Huang, X. and Moore, D. D. (2006) Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 312, 233-236.
115. Wang, X., Kiyokawa, H., Dennewitz, M. B. and Costa, R. H. (2002) The Forkhead Boxm1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration. Proc. Natl. Acad. Sci. USA 99, 16881-16886.
116. Das, A., Fernandez-Zapico, M. E., Cao, S., Yao, J., Fiorucci, S., Hebbel, R. P., Urrutia, R. and Shah, V. H. (2006) Disruption of an SP2/KLF6 repression complex by SHP is required for Farnesoid X receptor-induced endothelial cell migration. J. Biol. Chem. 28, 39105-39113.
117. Silva, J., Dasgupta, S., Wang, G., Krishnamurthy, K., Ritter, E. and Bieberich, E. (2006) Lipids isolated from bone induce the migration of human breast cancer cells. J. Lipid Res. 47, 724-733.
118. Bishop-Bailey, D., Walsh, D. T. and Warner, T. D. (2004) Expression and activation of the farnesoid X receptor in the vasculature. Proc. Natl. Acad. Sci. USA 101, 3668-3673.
119. Swales, K. E., Korbonits, M., Carpenter, R., Walsh, D. T., Warner, T. D. and Bishop-Bailey, D. (2006) The farnesoid X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression. Cancer Res. 66, 10120-10126.
120. Niesor, E. J., Flach, J., Lopes-Antoni, I., Perez, A. and Bentzen, C. L. (2001) The nuclear receptors FXR and LXRa: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. Curr. Pharm. Des. 7, 231-259.
121. De Gottardi, A., Dumonceau, J.-M., Bruttin, F., Vonlaufen, A., Morard, I., Spahr, L., Rubbia-Brandt, L., Frossard, J.-L., Dinjens, W., Rabinovitch, P. et al. (2006) Expression of the bile acid receptor FXR in Barretts esophagus and enhancement of apoptosis by guggulsterone in vitro. Mol. Cancer 5, 48.
122. He, F., Li, J., Mu, Y., Kuruba, R., Ma, Z., Wilson, A., Alber, S., Jiang, Y., Stevens, T., Watkins, S. et al. (2006) Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells. Circ. Res. 98, 192-199.
123. 2+ channels. J. Hypertens. Suppl. 6, S188-S191.
124. Galie, N., Manes, A. and Branzi, A. (2004) The endothelin system in pulmonary arterial hypertension. Cardiovasc. Res. 61, 227-237.