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Review

Farnesoid x receptor in human metabolism and disease: the interplay between gene polymorphisms, clinical phenotypes and disease susceptibility

, , , & , MSc PhD

Bibliography

  • Zhang Y, Kast-Woelbern HR, Edwards PA. Natural structural variants of the nuclear receptor farnesoid x receptor affect transcriptional activation. J Biol Chem 2003;278(1):104-10
  • Lee FY, Lee H, Hubbert ML, et al. FXR, a multipurpose nuclear receptor. Trends Biochem Sci 2006;31(10):572-80
  • Laffitte BA, Kast HR, Nguyen CM, et al. Identification of the DNA binding specificity and potential target genes for the farnesoid x-activated receptor. J Biol Chem 2000;275:10638-47
  • Shastry BS. SNPs: impact on gene function and phenotype. Methods Mol Biol 2009;578:3-22
  • Marzolini C, Tirona RG, Gervasini G, et al. A common polymorphism in the bile acid receptor farnesoid x receptor is associated with decreased hepatic target gene expression. Mol Endocrinol 2007;21:1769-80
  • Yu XQ, Xue CC, Wang G, et al. Multidrug resistance associated proteins as determining factors of pharmacokinetics and pharmacodynamics of drugs. Curr Drug Metab 2007;8:787-802
  • Wang YD, Chen WD, Moore DD, et al. FXR: a metabolic regulator and cell protector. Cell Res 2008;18:1087-95
  • Neimark E, Chen F, Li X, et al. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology 2004;40:149-56
  • Gadaleta RM, van Mil SW, Oldenburg B, et al. Bile acids and their nuclear receptor FXR: relevance for hepatobiliary and gastrointestinal disease. Biochim Biophys Acta 2010;1801:683-92
  • Lambert G, Amar MJ, Guo G, et al. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J Biol Chem 2003;278:2563-70
  • Insull WJr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J 2006;99:257-73
  • Teodoro JS, Rolo AP, Palmeira CM. Hepatic FXR: key regulator of whole-body energy metabolism. Trends Endocrinol Metab 2011;22:458-66
  • Matsukuma KE, Bennett MK, Huang J, et al. Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase. J Lipid Res 2006;47:2754-61
  • Hu M, To KK, Mak VW, et al. The ABCG2 transporter and its relations with the pharmacokinetics, drug interaction and lipid-lowering effects of statins. Expert Opin Drug Metab Toxicol 2011;7:49-62
  • Niemi M. Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 2010;87:130-3
  • Meyer Zu Schwabedissen HE, Bottcher K, Chaudhry A, et al. Liver x receptor alpha and farnesoid x receptor are major transcriptional regulators of OATP1B1. Hepatology 2010;52:1797-807
  • Hu M, Lui SS, Tam LS, et al. The farnesoid x receptor -1G > T polymorphism influences the lipid response to rosuvastatin. J Lipid Res 2012;53:1384-9
  • Ma K, Saha PK, Chan L, et al. Farnesoid x receptor is essential for normal glucose homeostasis. J Clin Invest 2006;116:1102-9
  • Cariou B, van Harmelen K, Duran-Sandoval D, et al. The farnesoid x receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem 2006;281:11039-49
  • Zhang Y, Lee FY, Barrera G, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci USA 2006;103:1006-11
  • Heni M, Wagner R, Ketterer C, et al. Genetic variation in NR1H4 encoding the bile acid receptor FXR determines fasting glucose and free fatty acid levels in humans. J Clin Endocrinol Metab 2013;98:E1224-9
  • Chignard N, Poupon R. Targeting farnesoid x receptor in hepatic and biliary inflammatory diseases. Gastroenterology 2009;137:734-5
  • D’ Aldebert E, Biyeyeme Bi Mve MJ, Mergey M, et al. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology 2009;136:1435-43
  • Liu Y, Binz J, Numerick MJ, et al. Hepatoprotection by the farnesoid x receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J Clin Invest 2003;112:1678-87
  • Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med 2004;10:1352-8
  • Wadsworth CA, Dixon PH, Wong JH, et al. Genetic factors in the pathogenesis of cholangiocarcinoma. Dig Dis 2011;29:93-7
  • Zhang S, Wang J, Liu Q, et al. Farnesoid x receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis. J Hepatol 2009;51:380-8
  • Kovacs P, Kress R, Rocha J, et al. Variation of the gene encoding the nuclear bile salt receptor FXR and gallstone susceptibility in mice and humans. J Hepatol 2008;48:116-24
  • Van Mil SW, Milona A, Dixon PH, et al. Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. Gastroenterology 2007;133:507-16
  • Inagaki T, Moschetta A, Lee YK, et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci USA 2006;103:3920-5
  • Attinkara R, Mwinyi J, Truninger K, et al. Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease. BMC Res Notes 2012;5:461
  • Nijmeijer RM, Gadaleta RM, van Mil SW, et al. Farnesoid x receptor (FXR) activation and FXR genetic variation in inflammatory bowel disease. PLoS One 2011;6:e23745
  • Gadaleta RM, van Erpecum KJ, Oldenburg B, et al. Farnesoid x receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 2011;60:463-72
  • Balesaria S, Pell RJ, Abbott LJ, et al. Exploring possible mechanisms for primary bile acid malabsorption: evidence for different regulation of ileal bile acid transporter transcripts in chronic diarrhoea. Eur J Gastroenterol Hepatol 2008;20:413-22
  • Montagnani M, Abrahamsson A, Galman C, et al. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption. World J Gastroenterol 2006;12:7710-14
  • Merk D, Steinhilber D, Schubert-Zsilavecz M. Medicinal chemistry of farnesoid x receptor ligands: from agonists and antagonists to modulators. Future Med Chem 2012;4:1015-36
  • Fiorucci S, Mencarelli A, Distrutti E, et al. Farnesoid x receptor: from medicinal chemistry to clinical applications. Future Med Chem 2012;4:877-91
  • Stanimirov B, Stankov K, Mikov M. Pleiotropic functions of bile acids mediated by the farnesoid x receptor. Acta Gastroenterol Belg 2012;75:389-98
  • Roda A, Pellicciari R, Gioiello A, et al. Semisynthetic bile acid FXR and TGR5 agonists: physicochemical properties, pharmacokinetics, and metabolism in the rat. J Pharmacol Exp Ther 2014;350:56-68
  • Zhan L, Liu HX, Fang Y, et al. Genome-wide binding and transcriptome analysis of human farnesoid x receptor in primary human hepatocytes. PLoS One 2014;9:e105930
  • Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid x receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013;145:574-82
  • Kowdley KV, Jones D, Luketic VA, et al. An international study evaluating the farnesoid x receptor agonist obeticholic acid as monotherapy in PBC. J Hepatol 2011;54:S13
  • Mason A, Luketic V, Lindor K, et al. Farnesoid x receptor agonists: a new class of drugs for the treatment of PBC? An international study evaluating the addition of INT-747 to ursodeoxycholic acid. J Hepatol 2010;52:S1
  • Neuschwander-Tetri BA. Farnesoid x receptor agonists: what they are and how they might be used in treating liver disease. Curr Gastroenterol Rep 2012;14:55-62
  • Schreuder TC, Marsman HA, Lenicek M, et al. The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance. Am J Physiol Gastrointest Liver Physiol 2010;298:G440-5
  • Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid x nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 2014. [ Epub ahead of print]
  • Zimmer V, Mullenbach R, Simon E, et al. Combined functional variants of hepatobiliary transporters and FXR aggravate intrahepatic cholestasis of pregnancy. Liver Int 2009;29:1286-8
  • Karlsen TH, Lie BA, Frey Froslie K, et al. Polymorphisms in the steroid and xenobiotic receptor gene influence survival in primary sclerosing cholangitis. Gastroenterology 2006;131:781-7
  • Zollner G, Wagner M, Fickert P, et al. Expression of bile acid synthesis and detoxification enzymes and the alternative bile acid efflux pump MRP4 in patients with primary biliary cirrhosis. Liver Int 2007;27:920-9
  • Trauner M. The nuclear bile acid receptor FXR as a novel therapeutic target in cholestatic liver diseases: hype or hope? Hepatology 2004;40:260-3
  • Wang YD, Chen WD, Wang M, et al. Farnesoid x receptor antagonizes nuclear factor kappaB in hepatic inflammatory response. Hepatology 2008;48:1632-43
  • Ito S, Fujimori T, Furuya A, et al. Impaired negative feedback suppression of bile acid synthesis in mice lacking betaKlotho. J Clin Invest 2005;115:2202-8

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