Liver X and farnesoid X receptors (LXR and FXR, nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [6]) are members of a steroid analogue-activated nuclear receptor subfamily, which form heterodimers with members of the retinoid X receptor family. Endogenous ligands for LXRs include hydroxycholesterols (OHC), while FXRs appear to be activated by bile acids. In humans and primates, NR1H5P is a pseudogene. However, in other mammals, it encodes a functional nuclear hormone receptor that appears to be involved in cholesterol biosynthesis [7].

T0901317 [10] and GW3965 [1] are synthetic agonists acting at both LXRα and LXRβ with less than 10-fold selectivity.

* Key recommended reading is highlighted with an asterisk

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Alawad AS, Levy C. (2016) FXR Agonists: From Bench to Bedside, a Guide for Clinicians. Dig. Dis. Sci., 61 (12): 3395-3404. [PMID:27734248]

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* Courtney R, Landreth GE. (2016) LXR Regulation of Brain Cholesterol: From Development to Disease. Trends Endocrinol. Metab., 27 (6): 404-414. [PMID:27113081]

Ding L, Yang L, Wang Z, Huang W. (2015) Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B, 5 (2): 135-44. [PMID:26579439]

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Faulds MH, Zhao C, Dahlman-Wright K. (2010) Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases. Curr Opin Pharmacol, 10 (6): 692-7. [PMID:20829110]

Fiorucci S, Cipriani S, Baldelli F, Mencarelli A. (2010) Bile acid-activated receptors in the treatment of dyslipidemia and related disorders. Prog. Lipid Res., 49 (2): 171-85. [PMID:19932133]

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Gabbi C, Warner M, Gustafsson JA. (2009) Minireview: liver X receptor beta: emerging roles in physiology and diseases. Mol. Endocrinol., 23 (2): 129-36. [PMID:19074550]

* Gadaleta RM, van Mil SW, Oldenburg B, Siersema PD, Klomp LW, van Erpecum KJ. (2010) Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease. Biochim. Biophys. Acta, 1801 (7): 683-92. [PMID:20399894]

Gardmo C, Tamburro A, Modica S, Moschetta A. (2011) Proteomics for the discovery of nuclear bile acid receptor FXR targets. Biochim. Biophys. Acta, 1812 (8): 836-41. [PMID:21439373]

Gonzalez-Sanchez E, Firrincieli D, Housset C, Chignard N. (2015) Nuclear receptors in acute and chronic cholestasis. Dig Dis, 33 (3): 357-66. [PMID:26045270]

Hageman J, Herrema H, Groen AK, Kuipers F. (2010) A role of the bile salt receptor FXR in atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 30 (8): 1519-28. [PMID:20631352]

Kemper JK. (2011) Regulation of FXR transcriptional activity in health and disease: Emerging roles of FXR cofactors and post-translational modifications. Biochim. Biophys. Acta, 1812 (8): 842-50. [PMID:21130162]

Krasowski MD, Ni A, Hagey LR, Ekins S. (2011) Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR. Mol. Cell. Endocrinol., 334 (1-2): 39-48. [PMID:20615451]

Kuipers F, Stroeve JH, Caron S, Staels B. (2007) Bile acids, farnesoid X receptor, atherosclerosis and metabolic control. Curr. Opin. Lipidol., 18 (3): 289-97. [PMID:17495603]

Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. (2009) Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev., 89 (1): 147-91. [PMID:19126757]

Maqdasy S, Trousson A, Tauveron I, Volle DH, Baron S, Lobaccaro JM. (2016) Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system. Mol. Aspects Med., 49: 31-46. [PMID:27091047]

Matsubara T, Li F, Gonzalez FJ. (2013) FXR signaling in the enterohepatic system. Mol. Cell. Endocrinol., 368 (1-2): 17-29. [PMID:22609541]

Mencarelli A, Fiorucci S. (2010) FXR an emerging therapeutic target for the treatment of atherosclerosis. J. Cell. Mol. Med., 14 (1-2): 79-92. [PMID:20041971]

* Merlen G, Ursic-Bedoya J, Jourdainne V, Kahale N, Glenisson M, Doignon I, Rainteau D, Tordjmann T. (2017) Bile acids and their receptors during liver regeneration: "Dangerous protectors". Mol. Aspects Med., 56: 25-33. [PMID:28302491]

* Moore DD, Kato S, Xie W, Mangelsdorf DJ, Schmidt DR, Xiao R, Kliewer SA. (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol. Rev., 58 (4): 742-59. [PMID:17132852]

* Mouzat K, Raoul C, Polge A, Kantar J, Camu W, Lumbroso S. (2016) Liver X receptors: from cholesterol regulation to neuroprotection-a new barrier against neurodegeneration in amyotrophic lateral sclerosis?. Cell. Mol. Life Sci., 73 (20): 3801-8. [PMID:27510420]

Schmuth M, Jiang YJ, Dubrac S, Elias PM, Feingold KR. (2008) Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology. J. Lipid Res., 49 (3): 499-509. [PMID:18182682]

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* Schulman IG. (2017) Liver X receptors link lipid metabolism and inflammation. FEBS Lett., 591 (19): 2978-2991. [PMID:28555747]

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Zollner G, Trauner M. (2009) Nuclear receptors as therapeutic targets in cholestatic liver diseases. Br. J. Pharmacol., 156 (1): 7-27. [PMID:19133988]

1. Collins JL, Fivush AM, Watson MA, Galardi CM, Lewis MC, Moore LB, Parks DJ, Wilson JG, Tippin TK, Binz JG, Plunket KD, Morgan DG, Beaudet EJ, Whitney KD, Kliewer SA, Willson TM. (2002) Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J. Med. Chem., 45 (10): 1963-6. [PMID:11985463]

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7. 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, Pääbo S, Mous J, Kremoser C, Deuschle U. (2003) Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Mol. Cell. Biol., 23 (3): 864-72. [PMID:12529392]

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10. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, Heyman RA, Dietschy JM, Mangelsdorf DJ. (2000) Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science, 289 (5484): 1524-9. [PMID:10968783]

11. Wu J, Xia C, Meier J, Li S, Hu X, Lala DS. (2002) The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol. Endocrinol., 16 (7): 1590-7. [PMID:12089353]

Subcommittee members: Donald P. McDonnell Department of Pharmacology and Cancer Biology Duke University School of Medicine C238A LSRC Box 3813 Durham, NC 27710 USA Rachid Safi Duke University School of Medicine C238A LSRC Box 3813 Durham, NC 27710 USA