Liver X and farnesoid X receptors (LXR and FXR, nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [1,7]) 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 [8].

T0901317 [11] and GW3965 [2] are synthetic agonists acting at both LXRα and LXRβ with less than 10-fold selectivity.

* Key recommended reading is highlighted with an asterisk

A-González N, Castrillo A. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim Biophys Acta, 1812 (8): 982-94. [PMID:21193033]

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

Bełtowski J, Semczuk A. (2010) Liver X receptor (LXR) and the reproductive system--a potential novel target for therapeutic intervention. Pharmacol Rep, 62 (1): 15-27. [PMID:20360612]

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Cariou B, Staels B. (2007) FXR: a promising target for the metabolic syndrome?. Trends Pharmacol Sci, 28 (5): 236-43. [PMID:17412431]

Chen WD, Wang YD, Meng Z, Zhang L, Huang W. (2011) Nuclear bile acid receptor FXR in the hepatic regeneration. Biochim Biophys Acta, 1812 (8): 888-92. [PMID:21167938]

Claudel T, Zollner G, Wagner M, Trauner M. (2011) Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease. Biochim Biophys Acta, 1812 (8): 867-78. [PMID:21194565]

* 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]

* El-Gendy BEM, Goher SS, Hegazy LS, Arief MMH, Burris TP. (2018) Recent Advances in the Medicinal Chemistry of Liver X Receptors. J Med Chem, 61 (24): 10935-10956. [PMID:30004226]

El-Hajjaji FZ, Oumeddour A, Pommier AJ, Ouvrier A, Viennois E, Dufour J, Caira F, Drevet JR, Volle DH, Baron S et al.. (2011) Liver X receptors, lipids and their reproductive secrets in the male. Biochim Biophys Acta, 1812 (8): 974-81. [PMID:21334438]

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]

Fiorucci S, Rizzo G, Donini A, Distrutti E, Santucci L. (2007) Targeting farnesoid X receptor for liver and metabolic disorders. Trends Mol Med, 13 (7): 298-309. [PMID:17588816]

Fiévet C, Staels B. (2009) Liver X receptor modulators: effects on lipid metabolism and potential use in the treatment of atherosclerosis. Biochem Pharmacol, 77 (8): 1316-27. [PMID:19101522]

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]

Schmuth M, Moosbrugger-Martinz V, Blunder S, Dubrac S. (2014) Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation. Biochim Biophys Acta, 1841 (3): 463-73. [PMID:24315978]

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

Wang YD, Chen WD, Moore DD, Huang W. (2008) FXR: a metabolic regulator and cell protector. Cell Res, 18 (11): 1087-95. [PMID:18825165]

Zhang Y, Edwards PA. (2008) FXR signaling in metabolic disease. FEBS Lett, 582 (1): 10-8. [PMID:18023284]

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

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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