Gene Symbol: NR1H3
Description: nuclear receptor subfamily 1 group H member 3
Alias: LXR-a, LXRA, RLD-1, oxysterols receptor LXR-alpha, liver X nuclear receptor alpha variant 1
Species: human
Products:     NR1H3

Top Publications

  1. Korf H, Vander Beken S, Romano M, Steffensen K, Stijlemans B, Gustafsson J, et al. Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice. J Clin Invest. 2009;119:1626-37 pubmed publisher
    ..Furthermore, mice deficient in both LXR isoforms, LXRalpha and LXRbeta (Lxra-/-Lxrb-/- mice), were more susceptible to infection, developing higher bacterial burdens and an increase in the ..
  2. Dahlman I, Nilsson M, Gu H, Lecoeur C, Efendic S, Ostenson C, et al. Functional and genetic analysis in type 2 diabetes of liver X receptor alleles--a cohort study. BMC Med Genet. 2009;10:27 pubmed publisher
    Liver X receptor alpha (LXRA) and beta (LXRB) regulate glucose and lipid homeostasis in model systems but their importance in human physiology is poorly understood...
  3. Ketterer C, Müssig K, Machicao F, Stefan N, Fritsche A, Haring H, et al. Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes. J Mol Med (Berl). 2011;89:75-81 pubmed publisher
    ..We hypothesized that common variants in the NR1H2 and NR1H3 genes, encoding LXR-β and -α, respectively, may alter pancreatic β-cell function...
  4. Cui G, Qin X, Wu L, Zhang Y, Sheng X, Yu Q, et al. Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J Clin Invest. 2011;121:658-70 pubmed publisher
    ..This study reports what we believe to be a novel signaling pathway underlying LXR-mediated regulation of Th17 cell differentiation and autoimmunity. ..
  5. Legry V, Cottel D, Ferrieres J, Chinetti G, Deroide T, Staels B, et al. Association between liver X receptor alpha gene polymorphisms and risk of metabolic syndrome in French populations. Int J Obes (Lond). 2008;32:421-8 pubmed publisher
    ..The liver X receptor alpha (NR1H3) plays numerous roles in metabolic pathways involved in metabolic syndrome...
  6. Dahlman I, Nilsson M, Jiao H, Hoffstedt J, Lindgren C, Humphreys K, et al. Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity. Pharmacogenet Genomics. 2006;16:881-9 pubmed
    b>LXRA and LXRB genes regulate adiposity, energy dissipation, as well as glucose and lipid homeostasis in mice. We investigated the LXR genes in human obesity...
  7. Rébé C, Raveneau M, Chevriaux A, Lakomy D, Sberna A, Costa A, et al. Induction of transglutaminase 2 by a liver X receptor/retinoic acid receptor alpha pathway increases the clearance of apoptotic cells by human macrophages. Circ Res. 2009;105:393-401 pubmed publisher
    ..A combination of LXR/RARalpha agonists that may operate in atherosclerosis could also constitute a promising strategy to improve the clearance of apoptotic cells by macrophages in other pathological situations. ..
  8. Cozzone D, Debard C, Dif N, Ricard N, Disse E, Vouillarmet J, et al. Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells. Diabetologia. 2006;49:990-9 pubmed
    ..However, the long-term consequences of triglyceride accumulation in muscle should be evaluated before the development of effective LXR-based therapeutic agents. ..
  9. Tang S, Chen W, Yin K, Zhao G, Mo Z, Lv Y, et al. PAPP-A negatively regulates ABCA1, ABCG1 and SR-B1 expression by inhibiting LXR? through the IGF-I-mediated signaling pathway. Atherosclerosis. 2012;222:344-54 pubmed publisher
    ..Therefore, our study provided one of the mechanisms for understanding the critical effect of PAPP-A in pathogenesis of atherosclerosis...

More Information


  1. Watanabe K, Sakurai K, Tsuchiya Y, Yamazoe Y, Yoshinari K. Dual roles of nuclear receptor liver X receptor α (LXRα) in the CYP3A4 expression in human hepatocytes as a positive and negative regulator. Biochem Pharmacol. 2013;86:428-36 pubmed publisher
    ..Therefore, nutritional, physiological and disease conditions affecting LXRα might be one of the determinants for the basal and xenobiotic-responsive expression of CYP3A4 in human livers. ..
  2. Nedumaran B, Kim G, Hong S, Yoon Y, Kim Y, Lee C, et al. Orphan nuclear receptor DAX-1 acts as a novel corepressor of liver X receptor alpha and inhibits hepatic lipogenesis. J Biol Chem. 2010;285:9221-32 pubmed publisher
    ..Overall, this study suggests that DAX-1, a novel corepressor of LXRalpha, functions as a negative regulator of lipogenic enzyme gene expression in liver. ..
  3. Ou Z, Wada T, Gramignoli R, Li S, Strom S, Huang M, et al. MicroRNA hsa-miR-613 targets the human LXRα gene and mediates a feedback loop of LXRα autoregulation. Mol Endocrinol. 2011;25:584-96 pubmed publisher
  4. Birrell M, Catley M, Hardaker E, Wong S, Willson T, McCluskie K, et al. Novel role for the liver X nuclear receptor in the suppression of lung inflammatory responses. J Biol Chem. 2007;282:31882-90 pubmed
    ..Therefore, data suggest that LXR ligands have utility in the treatment of lung diseases that involves chronic inflammation mediated by macrophages and neutrophils. ..
  5. Delvecchio C, Bilan P, Radford K, Stephen J, Trigatti B, Cox G, et al. Liver X receptor stimulates cholesterol efflux and inhibits expression of proinflammatory mediators in human airway smooth muscle cells. Mol Endocrinol. 2007;21:1324-34 pubmed
    ..Our findings reveal biological roles for LXR in ASM cells and suggest that modulation of LXR activity offers prospects for new therapeutic approaches in the treatment of asthma and other inflammatory respiratory diseases...
  6. Jakobsson T, Venteclef N, Toresson G, Damdimopoulos A, Ehrlund A, Lou X, et al. GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus. Mol Cell. 2009;34:510-8 pubmed publisher
    ..The pathway and coregulator selectivity of this mechanism implies pharmacological possibilities for the development of selective LXR agonists...
  7. Willy P, Umesono K, Ong E, Evans R, Heyman R, Mangelsdorf D. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 1995;9:1033-45 pubmed
    ..Thus, the interaction with LXR alpha shifts RXR from its role described previously as a silent, DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXREs. ..
  8. Natunen T, Helisalmi S, Vepsäläinen S, Sarajärvi T, Antikainen L, Mäkinen P, et al. Genetic analysis of genes involved in amyloid-? degradation and clearance in Alzheimer's disease. J Alzheimers Dis. 2012;28:553-9 pubmed publisher
    ..Here, we selected 12 genes (MMEL1, ECE1, ECE2, AGER, PLG, PLAT, NR1H3, MMP3, LRP1, TTR, NR1H2, and MMP9) involved in A? catabolism on the basis of PubMed-based literature search and ..
  9. Chinetti Gbaguidi G, Baron M, Bouhlel M, Vanhoutte J, Copin C, Sebti Y, et al. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPAR? and LXR? pathways. Circ Res. 2011;108:985-95 pubmed publisher
    ..These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPAR?-LXR? pathways. ..
  10. Venkateswaran A, Laffitte B, Joseph S, Mak P, Wilpitz D, Edwards P, et al. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci U S A. 2000;97:12097-102 pubmed
    ..These findings have important implications for our understanding of mammalian cholesterol homeostasis and suggest new opportunities for pharmacological regulation of cellular lipid metabolism. ..
  11. Peet D, Turley S, Ma W, Janowski B, Lobaccaro J, Hammer R, et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell. 1998;93:693-704 pubmed
    ..These results demonstrate the existence of a physiologically significant feed-forward regulatory pathway for sterol metabolism and establish the role of LXR alpha as the major sensor of dietary cholesterol. ..
  12. Watanabe Y, Jiang S, Takabe W, Ohashi R, Tanaka T, Uchiyama Y, et al. Expression of the LXRalpha protein in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2005;25:622-7 pubmed
    ..In the human body, the LXRalpha protein is highly expressed in macrophage lineage cells and foam cells in atherosclerotic lesions and is identified as a target for intervention in atherosclerotic disease. ..
  13. Chinetti G, Lestavel S, Bocher V, Remaley A, Neve B, Torra I, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 2001;7:53-8 pubmed
    ..Here we identify a regulatory role for PPAR-alpha and PPAR-gamma in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages...
  14. Schultz J, Tu H, Luk A, Repa J, Medina J, Li L, et al. Role of LXRs in control of lipogenesis. Genes Dev. 2000;14:2831-8 pubmed
    ..Complementary studies in cell culture and animals suggested that the increase in plasma lipids occurs via LXR-mediated induction of the sterol regulatory element-binding protein 1 (SREBP-1) lipogenic program. ..
  15. Ghisletti S, Huang W, Ogawa S, Pascual G, Lin M, Willson T, et al. Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell. 2007;25:57-70 pubmed
    ..These studies define parallel but functionally distinct pathways that are utilized by PPARgamma and LXRs to differentially regulate complex programs of gene expression that control immunity and homeostasis. ..
  16. Li N, Salter R, Ramji D. Molecular mechanisms underlying the inhibition of IFN-?-induced, STAT1-mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs. J Cell Biochem. 2011;112:675-83 pubmed publisher
    ..These studies reveal differences in the mechanism of action of agonists of PPARs (and simvastatin) and LXRs on the IFN-?-induced, STAT1-mediated gene transcription in human macrophages. ..
  17. Li X, Zhang S, Blander G, Tse J, Krieger M, Guarente L. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007;28:91-106 pubmed
    ..Our findings suggest that deacetylation of LXRs by SIRT1 may be a mechanism that affects atherosclerosis and other aging-associated diseases. ..
  18. Phelan C, Weaver J, Steger D, Joshi S, Maslany J, Collins J, et al. Selective partial agonism of liver X receptor alpha is related to differential corepressor recruitment. Mol Endocrinol. 2008;22:2241-9 pubmed publisher
    ..Thus, differential recruitment of NCoR is a major determinant of partial agonism and selective LXR modulation of target genes...
  19. Torra I, Ismaili N, Feig J, Xu C, Cavasotto C, Pancratov R, et al. Phosphorylation of liver X receptor alpha selectively regulates target gene expression in macrophages. Mol Cell Biol. 2008;28:2626-36 pubmed publisher
    ..Thus, our findings reveal a previously unrecognized role for phosphorylation in restricting the repertoire of LXRalpha-responsive genes. ..
  20. Ishibashi M, Filomenko R, Rébé C, Chevriaux A, Varin A, Derangère V, et al. Knock-down of the oxysterol receptor LXR? impairs cholesterol efflux in human primary macrophages: lack of compensation by LXR? activation. Biochem Pharmacol. 2013;86:122-9 pubmed publisher
    ..In contrast to earlier mouse studies, LXR? levels appear as a limiting factor for macrophage cholesterol efflux in humans. ..
  21. Legry V, Bokor S, Beghin L, Galfo M, Gonzalez Gross M, Molnar D, et al. Associations between common genetic polymorphisms in the liver X receptor alpha and its target genes with the serum HDL-cholesterol concentration in adolescents of the HELENA Study. Atherosclerosis. 2011;216:166-9 pubmed publisher
    Genetic variability in the NR1H3 gene (encoding LXR?) and in several of its target genes is associated with serum HDL-cholesterol (HDL-C) concentrations. We sought to assess if these associations could be detected in adolescents.
  22. Delvecchio C, Capone J. Protein kinase C alpha modulates liver X receptor alpha transactivation. J Endocrinol. 2008;197:121-30 pubmed publisher
    ..Our findings reveal a mode of regulation of LXRalpha that may be relevant to disease conditions where aberrant PKC signaling is observed, such as diabetes. ..
  23. Laffitte B, Repa J, Joseph S, Wilpitz D, Kast H, Mangelsdorf D, et al. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci U S A. 2001;98:507-12 pubmed
    ..Together with our previous work, these findings support a central role for LXR signaling pathways in the control of macrophage cholesterol efflux through the coordinate regulation of apoE, ABCA1, and ABCG1 expression...
  24. Robitaille J, Houde A, Lemieux S, Gaudet D, Perusse L, Vohl M. The lipoprotein/lipid profile is modulated by a gene-diet interaction effect between polymorphisms in the liver X receptor-alpha and dietary cholesterol intake in French-Canadians. Br J Nutr. 2007;97:11-8 pubmed
    ..Similar results were observed for c.-840C>A and c.-1830T>C. These results suggest that cholesterol intake interacts with LXRalpha variants to modulate the plasma lipid profile. ..
  25. Wang Y, Moser A, Shigenaga J, Grunfeld C, Feingold K. Downregulation of liver X receptor-alpha in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines. J Lipid Res. 2005;46:2377-87 pubmed
  26. Lehmann J, Kliewer S, Moore L, Smith Oliver T, Oliver B, Su J, et al. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 1997;272:3137-40 pubmed
    ..Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXRs play a critical role in the regulation of cholesterol homeostasis. ..
  27. Ogawa S, Lozach J, Benner C, Pascual G, Tangirala R, Westin S, et al. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell. 2005;122:707-21 pubmed
    ..These findings reveal combinatorial control of homeostasis and immune responses by nuclear receptors and suggest new approaches for treatment of inflammatory diseases. ..
  28. Henry Berger J, Mouzat K, Baron S, Bernabeu C, Marceau G, Saru J, et al. Endoglin (CD105) expression is regulated by the liver X receptor alpha (NR1H3) in human trophoblast cell line JAR. Biol Reprod. 2008;78:968-75 pubmed publisher
    ..In the present study, we show that the endoglin (ENG) gene is a direct target of the liver X receptor alpha (NR1H3, also known as LXRalpha)...
  29. Sparrow C, Baffic J, Lam M, Lund E, Adams A, Fu X, et al. A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. J Biol Chem. 2002;277:10021-7 pubmed
    ..The present work shows that the acetyl-podocarpic dimer (APD) is a potent, selective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2)...
  30. Wang Z, Sadovnick A, Traboulsee A, Ross J, Bernales C, Encarnacion M, et al. Case-Control Studies Are Not Familial Studies. Neuron. 2016;92:339-341 pubmed publisher
    ..We recently published a study proposing a rare variant in the NR1H3 gene (p...
  31. Miyata K, McCaw S, Patel H, Rachubinski R, Capone J. The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling. J Biol Chem. 1996;271:9189-92 pubmed
    ..These findings identify a novel partner for PPARalpha and suggest that LXRalpha plays a role in modulating PPAR-signaling pathways in the cell. ..
  32. Lu Y, Jia Y. Quercetin upregulates ABCA1 expression through liver X receptor alpha signaling pathway in THP-1 macrophages. Eur Rev Med Pharmacol Sci. 2016;20:3945-3952 pubmed
    ..In this study, we try to explore whether quercetin up-regulates LXRa-mediated ABCA1 expression. THP-1 cells were cultured...
  33. Sharma K, Misra S, Kumar A, Mittal B. Association of liver X receptors (LXRs) genetic variants to gallbladder cancer susceptibility. Tumour Biol. 2013;34:3959-66 pubmed publisher
    ..Our results suggest that LXR-? polymorphisms influence gallbladder cancer susceptibility through estrogen and gallstone-dependent pathways. ..
  34. Zhong D, Zhang Y, Zeng Y, Gao M, Wu G, Hu C, et al. MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXR?. Lipids Health Dis. 2013;12:32 pubmed publisher
    ..MiR-613 suppresses lipogenesis by directly targeting LXR? in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis. ..
  35. Zhao Y, Li L, Ma J, Chen G, Bai J. LXRalpha gene downregulation by lentiviral-based RNA interference enhances liver function after fatty liver transplantation in rats. Hepatobiliary Pancreat Dis Int. 2015;14:386-93 pubmed
    ..05). LXRalpha-RNAi-LV treatment significantly downregulated LXRalpha expression and improve steatotic liver graft function and recipient survival after a fatty liver transplantation in rats. ..
  36. Bedi S, Hines G, Lozada Fernandez V, de Jesus Piva C, Kaliappan A, Rider S, et al. Fatty acid binding profile of the liver X receptor α. J Lipid Res. 2017;58:393-402 pubmed publisher
    ..Transactivation assays showed that MCFA activated LXRα, whereas long-chain FA caused no effect. Our results suggest that LXRα functions as a receptor for saturated FA or acyl-CoA of C10 and C12 in length. ..
  37. Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou J, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes. 1997;46:1319-27 pubmed
    ..These results indicated that obesity is not associated with alteration in PPAR gene expression in abdominal subcutaneous adipose tissue in humans. ..
  38. Chang Y, Zhao Y, Cao Y, Gu X, Li Z, Wang S, et al. Liver X receptor α inhibits osteosarcoma cell proliferation through up-regulation of FoxO1. Cell Physiol Biochem. 2013;32:180-6 pubmed publisher
    ..LXRα activates FoxO1 transcription through a direct binding on its promoter region. LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment. ..
  39. Lee T, Pan C, Peng C, Kou Y, Chen C, Ching L, et al. Anti-atherogenic effect of berberine on LXRalpha-ABCA1-dependent cholesterol efflux in macrophages. J Cell Biochem. 2010;111:104-10 pubmed publisher
    ..These data suggest that berberine abrogates the formation of foam cells by macrophages by enhancing LXRalpha-ABCA1-dependent cholesterol efflux...
  40. Youlin K, Li Z, Weiyang H, Jian K, Siming L, Xin G. Liver X receptor activation inhibits PC-3 prostate cancer cells via the beta-catenin pathway. Pathol Res Pract. 2017;213:267-270 pubmed publisher
    ..Meanwhile, the expression of beta-catenin target gene cyclin D1 and c-MYC were also decreased. This study provided additional evidence that LXR activation inhibited PC-3 prostate cancer cells via suppressing beta-catenin pathway. ..
  41. Rahman S, Baquero K, Choudhury M, Janssen R, de la Houssaye B, Sun M, et al. C/EBP? in bone marrow is essential for diet induced inflammation, cholesterol balance, and atherosclerosis. Atherosclerosis. 2016;250:172-9 pubmed publisher
    ..C/EBP? in hematopoietic cells is crucial to regulate diet-induced inflammation, hyperlipidemia and atherosclerosis development. ..
  42. Tejera N, Vauzour D, Betancor M, Sayanova O, Usher S, Cochard M, et al. A Transgenic Camelina sativa Seed Oil Effectively Replaces Fish Oil as a Dietary Source of Eicosapentaenoic Acid in Mice. J Nutr. 2016;146:227-35 pubmed publisher
    ..005) expressions were induced by CO. No impact of treatment on liver X receptor α (Lxra) or sterol regulatory element-binding protein 1c (Srebp1c) was evident...
  43. Gondcaille C, Genin E, Lopez T, Dias A, Geillon F, Andreoletti P, et al. LXR antagonists induce ABCD2 expression. Biochim Biophys Acta. 2014;1841:259-66 pubmed
    ..we show by multiple tissue expression array that expression of ABCD2 appears to be inversely correlated with NR1H3 (LXRalpha) expression...
  44. Hong I, Rho H, Kim D, Lee M. Activation of LXR? induces lipogenesis in HaCaT cells. Arch Pharm Res. 2010;33:1443-9 pubmed publisher
    The oxysterol nuclear receptors, LXR? (liver X receptor ?; NR1H3) and LXR? (NR1H2), coordinately regulate the expression of genes involved in lipid metabolism, anti-inflammation, and cholesterol transport...
  45. Kim H, Cho H, Kim H, Cheong J. Oxygenated derivatives of cholesterol promote hepatitis B virus gene expression through nuclear receptor LXR? activation. Virus Res. 2011;158:55-61 pubmed publisher
    ..These results point to a novel mechanism of oxysterol-mediated gene regulation in HBV replication and a potent mechanism underlying the failure of IFN?-based treatment. ..
  46. Honzumi S, Shima A, Hiroshima A, Koieyama T, Ubukata N, Terasaka N. LXRalpha regulates human CETP expression in vitro and in transgenic mice. Atherosclerosis. 2010;212:139-45 pubmed publisher
    ..These findings indicate that LXRalpha has an essential role in the regulation of CETP expression and maintaining RCT. ..
  47. Gjevestad G, Ottestad I, Biong A, Iversen P, Retterstøl K, Raastad T, et al. Consumption of protein-enriched milk has minor effects on inflammation in older adults-A 12-week double-blind randomized controlled trial. Mech Ageing Dev. 2017;162:1-8 pubmed publisher
    ..Significant differences in the mRNA expression of nuclear receptor subfamily, group H, member 3 (NR1H3, encoding the LXRα transcription factor) and interferon gamma (INFG) were observed between groups...
  48. Walcher D, Vasic D, Heinz P, Bach H, Durst R, Hausauer A, et al. LXR activation inhibits chemokine-induced CD4-positive lymphocyte migration. Basic Res Cardiol. 2010;105:487-94 pubmed publisher
    ..Given the crucial importance of chemokine-induced T cell migration in early atherogenesis, LXR activators may be promising tools to modulate this effect. ..
  49. Pommier A, Alves G, Viennois E, Bernard S, Communal Y, Sion B, et al. Liver X Receptor activation downregulates AKT survival signaling in lipid rafts and induces apoptosis of prostate cancer cells. Oncogene. 2010;29:2712-23 pubmed publisher
    ..Altogether, pharmacological modulation of LXR activity could thus reduce prostate tumor growth by enhancing apoptosis in a lipid raft-dependent manner...
  50. Byun H, Hong E, Park S, Koh D, Choi M, Jang H, et al. Pravastatin activates the expression of farnesoid X receptor and liver X receptor alpha in Hep3B cells. Hepatobiliary Pancreat Dis Int. 2014;13:65-73 pubmed
  51. Gbaguidi G, Agellon L. The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter. Biochim Biophys Acta. 2002;1583:229-36 pubmed
    ..Peroxisome proliferator-activated receptor alpha (PPARalpha; NR1C1) and liver X receptor alpha (LXRalpha; NR1H3) are two nuclear receptors that stimulate the murine Cyp7a1 gene...
  52. Thomassen M, Barna B, Malur A, Bonfield T, Farver C, Malur A, et al. ABCG1 is deficient in alveolar macrophages of GM-CSF knockout mice and patients with pulmonary alveolar proteinosis. J Lipid Res. 2007;48:2762-8 pubmed
    ..These findings document the existence of ABCG1 deficiency in human lung disease and highlight a critical role for ABCG1 in surfactant homeostasis...
    ..Taken together, our data demonstrates that intact hydrophobic interactions and salt bridges at the interface mediate efficient ligand-dependent transactivation activities...
  54. Mehrotra A, Kaul D, Joshi K. LXR-? selectively reprogrammes cancer cells to enter into apoptosis. Mol Cell Biochem. 2011;349:41-55 pubmed publisher
    ..On the basis of this study we propose that in near future LXR-? agonist (Withaferin A) may definitely find its use in the therapeutic interventions directed towards the treatment of cancer. ..
  55. Ning Y, Bai Q, Lu H, Li X, Pandak W, Zhao F, et al. Overexpression of mitochondrial cholesterol delivery protein, StAR, decreases intracellular lipids and inflammatory factors secretion in macrophages. Atherosclerosis. 2009;204:114-20 pubmed publisher
    ..These effects can prevent macrophage apoptosis. These results imply a potential role of StAR in the prevention of atherosclerosis...
  56. Gao M, Zeng Y, Guan Y, Hu Z, Zhong D, Shen X, et al. Activation of liver X receptor attenuates endothelin-1 expression in vascular endothelial cells. Int J Biochem Cell Biol. 2012;44:2299-307 pubmed publisher
    ..These results suggest that LXRs may serve as a novel molecular target for modulating ET-1 expression in VECs, and even for the treatment of ET-1-associated inflammatory diseases. ..
  57. Wang Z, Sadovnick A, Traboulsee A, Ross J, Bernales C, Encarnacion M, et al. Nuclear Receptor NR1H3 in Familial Multiple Sclerosis. Neuron. 2016;90:948-54 pubmed publisher
    ..In this study, we describe the identification of NR1H3 p...
  58. Jiang M, Xu M, Ren S, Selcer K, Xie W. Transgenic Overexpression of Steroid Sulfatase Alleviates Cholestasis. Liver Res. 2017;1:63-69 pubmed publisher
    ..The conversion of sulfated oxysterols to their non-sulfated counterparts is catalyzed by STS. The aim of this study is to determine whether STS can alleviate cholestasis by increasing the activity of LXR...
  59. Mak P, Laffitte B, Desrumaux C, Joseph S, Curtiss L, Mangelsdorf D, et al. Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta. J Biol Chem. 2002;277:31900-8 pubmed
    ..These results suggest an alternative mechanism by which lipids are removed from macrophage foam cells. ..
  60. Ji L, Zhang B, Zhao G. Liver X receptor ? (LXR?) promoted invasion and EMT of gastric cancer cells by regulation of NF-?B activity. Hum Cell. 2017;30:124-132 pubmed publisher
    ..Collectively, our results indicated that down-regulation of LXR? was shown to suppress invasion and EMT of GC cells by decreasing the expressions of related proteins through inhibiting the PI3K/Akt/NF-?B signaling pathway. ..
  61. Savic D, Ramaker R, Roberts B, Dean E, Burwell T, Meadows S, et al. Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation. Genome Med. 2016;8:74 pubmed publisher
    The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis...
  62. Reyes Quiroz M, Alba G, Saenz J, Geniz I, Jimenez J, Martín Nieto J, et al. Platelet-activating factor and hydrogen peroxide exert a dual modulatory effect on the transcription of LXR? and its target genes in human neutrophils. Int Immunopharmacol. 2016;38:357-66 pubmed publisher
    ..In summary, our results show that H2O2, either exogenous or PAF-induced, exerts a dual regulation on mRNA expression of LXR? and its target genes. ..
  63. Ford C, Sherratt M, Griffiths C, Watson R. Liver X receptor ?: maintenance of epidermal expression in intrinsic and extrinsic skin aging. Age (Dordr). 2009;31:365-72 pubmed publisher
    ..75). Our data therefore suggest that, while not playing a major role in skin aging, robust cutaneous expression implies a fundamental role for LXR? in epidermal biology. ..
  64. Li J, Zhang S. microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2. Biochem Biophys Res Commun. 2016;476:218-224 pubmed publisher
    ..The suppressive effects of miR-150 on macrophage foam cell formation are mediated through targeting of AdipoR2. Delivery of miR-150 may represent a potential approach to prevent macrophage foam cell formation in atherosclerosis. ..
  65. Fan A, Wang Q, Yuan Y, Cheng J, Chen L, Guo X, et al. Liver X receptor-α and miR-130a-3p regulate expression of sphingosine 1-phosphate receptor 2 in human umbilical vein endothelial cells. Am J Physiol Cell Physiol. 2016;310:C216-26 pubmed publisher
    ..These results suggest that LXR-α might downregulate S1PR2 expression via miR-130a-3p in quiescent HUVECs. Stimulation of TNF-α attenuates the activity of LXR-α and results in enhanced S1PR2 expression. ..
  66. Cannon M, Silljé H, Sijbesma J, Vreeswijk Baudoin I, Ciapaite J, van der Sluis B, et al. Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization. EMBO Mol Med. 2015;7:1229-43 pubmed publisher
  67. Hong I, Lee M, Na T, Zouboulis C, Lee M. LXRalpha enhances lipid synthesis in SZ95 sebocytes. J Invest Dermatol. 2008;128:1266-72 pubmed
    ..Thus, we suggest that LXR ligands could provide a new class of therapeutic agents for sebaceous gland-associated disorders such as seborrhea and acne. ..
  68. Trogan E, Feig J, Dogan S, Rothblat G, Angeli V, Tacke F, et al. Gene expression changes in foam cells and the role of chemokine receptor CCR7 during atherosclerosis regression in ApoE-deficient mice. Proc Natl Acad Sci U S A. 2006;103:3781-6 pubmed
    ..Taken with the other gene expression data, these results in vivo point to complex relationships among the immune system, nuclear hormone receptors, and inflammation during regression...
  69. Du C, Shi Y, Ren Y, Wu H, Yao F, Wei J, et al. Anthocyanins inhibit high-glucose-induced cholesterol accumulation and inflammation by activating LXRα pathway in HK-2 cells. Drug Des Devel Ther. 2015;9:5099-113 pubmed publisher
    ..Collectively, these findings suggest that blocking cholesterol deposition and inhibiting the LXRα pathway-induced inflammatory response might be one of the main mechanisms by which anthocyanins exert their protective effects in DN. ..
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    ..Our data lend further experimental support to the hypothesis that LXRbeta-selective agonists may raise HDL-cholesterol and stimulate macrophage cholesterol efflux without causing liver triglyceride accumulation...
  71. Jeong S, Kim S, Park J, Jung I, Lee M, Jeon S, et al. Prdx1 (peroxiredoxin 1) deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux. Autophagy. 2017;:1-14 pubmed publisher excessive oxidative stress, resulting in the inhibition of free cholesterol formation and the reduction of NR1H3 (nuclear receptor subfamily 1, group H, member 3) activity...
  72. Morbitzer D, Namgaladze D, Brüne B. Phospholipase A(2)-modified low-density lipoprotein activates liver X receptor in human macrophages. Cell Biochem Biophys. 2012;63:143-9 pubmed publisher
    ..A concomitantly increased cholesterol efflux may prevent excessive cholesterol accumulation and thus, attenuate foam cell formation...
  73. Plosch T, van der Veen J, Havinga R, Huijkman N, Bloks V, Kuipers F. Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice. Am J Physiol Gastrointest Liver Physiol. 2006;291:G414-23 pubmed
    ..of Abcg5 and Abcg8 was strongly induced (fivefold and fourfold) in wild-type but not LXR-alpha-deficient (Lxra(-/-)) mice. Surprisingly, hepatobiliary cholesterol excretion was increased to the same extent, i.e., 2...
  74. Nanthirudjanar T, Furumoto H, Hirata T, Sugawara T. Oxidized eicosapentaenoic acids more potently reduce LXR?-induced cellular triacylglycerol via suppression of SREBP-1c, PGC-1? and GPA than its intact form. Lipids Health Dis. 2013;12:73 pubmed publisher
    ..Therefore, the advantageous effects of OEPAs on cardiovascular diseases might be due to their SREBP-1c, PGC-1? and GPA mediated ameliorating effects. ..
  75. Xu G, Li H, Pan L, Shang Q, Honda A, Ananthanarayanan M, et al. FXR-mediated down-regulation of CYP7A1 dominates LXRalpha in long-term cholesterol-fed NZW rabbits. J Lipid Res. 2003;44:1956-62 pubmed
    ..Thus, in rabbits, when FXR and LXRalpha are activated simultaneously, the inhibitory effect of FXR overrides the stimulatory effect of LXRalpha to suppress CYP7A1 mRNA expression...
  76. Wang L, Zhang N, Wang Z, Ai D, Cao Z, Pan H. Decreased MiR-155 Level in the Peripheral Blood of Non-Alcoholic Fatty Liver Disease Patients may Serve as a Biomarker and may Influence LXR Activity. Cell Physiol Biochem. 2016;39:2239-2248 pubmed
    ..In summary, decreased expression of miR-155 in the peripheral blood may be utilized as a potential novel biomarker for NAFLD screening mainly by targeting LXRα. ..
  77. Fongsupa S, Soodvilai S, Muanprasat C, Chatsudthipong V, Soodvilai S. Activation of liver X receptors inhibits cadmium-induced apoptosis of human renal proximal tubular cells. Toxicol Lett. 2015;236:145-53 pubmed publisher
    ..This study provides the first evidence to show LXR activation reduces cadmium-induced apoptotic cell death of human renal proximal tubular cells by inhibition of ROS production and JNK activation. ..
  78. Zhao C, Dahlman Wright K. Liver X receptor in cholesterol metabolism. J Endocrinol. 2010;204:233-40 pubmed publisher
    ..There are two isoforms of LXR, LXRalpha (NR1H3) and LXRbeta (NR1H2)...
  79. Brauner R, Johannes C, Ploessl F, Bracher F, Lorenz R. Phytosterols reduce cholesterol absorption by inhibition of 27-hydroxycholesterol generation, liver X receptor ? activation, and expression of the basolateral sterol exporter ATP-binding cassette A1 in Caco-2 enterocytes. J Nutr. 2012;142:981-9 pubmed publisher
    ..This local LXR? antagonism of dietary phytosterols contributes to sterol selectivity and reduces fractional cholesterol absorption and preloading of nascent HDL with dietary cholesterol...
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    ..In addition, we discuss the challenges that need to be overcome before an LXR modulator can reach clinical use. ..