liver x receptors

Summary

Summary: Nuclear receptors that bind OXYSTEROLS and function as heterodimers with RETINOID X RECEPTORS. They have important functions in regulating cholesterol homeostasis, ENERGY METABOLISM; INFLAMMATION; and the immune response.

Top Publications

  1. Polyzos S, Kountouras J, Mantzoros C. Sulfated oxysterols as candidates for the treatment of nonalcoholic fatty liver disease. Metabolism. 2012;61:755-8 pubmed publisher
  2. Sviridov D. Many ABCs make light work with cholesterol. Aging (Albany NY). 2013;5:637-8 pubmed
  3. Kim B, Son Y, Choi J, Eo S, Park Y, Kim K. 27-Hydroxycholesterol upregulates the production of heat shock protein 60 of monocytic cells. J Steroid Biochem Mol Biol. 2017;172:29-35 pubmed publisher
    ..Results of the current study indicate that 27OHChol upregulates not only cell-surface and cellular levels of HSP60 but also its release from monocytic cells, thereby contributing to activation of the immune system. ..
  4. Xu J, Feng Y, Liu L, Wang W, Zhong X, Wei X, et al. Liver X Receptor ? Is Involved in Counteracting Mechanical Allodynia by Inhibiting Neuroinflammation in the Spinal Dorsal Horn. Anesthesiology. 2017;127:534-547 pubmed publisher
    b>Liver X receptors, including ? and ? isoforms, are ligand-activated transcription factors. Whether liver X receptor ? plays a role in neuropathic pain is unknown. A spared nerve injury model was established in adult male rats and mice...
  5. Errico T, Méndez Lara K, Santos D, Cabrerizo N, Baila Rueda L, Metso J, et al. LXR-dependent regulation of macrophage-specific reverse cholesterol transport is impaired in a model of genetic diabesity. Transl Res. 2017;186:19-35.e5 pubmed publisher
  6. Schulman I. Liver X receptors link lipid metabolism and inflammation. FEBS Lett. 2017;591:2978-2991 pubmed publisher
    ..Indeed, in many cases changes in metabolism appear to be necessary for a robust immune response. The Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that regulate gene networks controlling ..
  7. Lee S, Tontonoz P. Liver X receptors at the intersection of lipid metabolism and atherogenesis. Atherosclerosis. 2015;242:29-36 pubmed publisher
  8. Ducheix S, Montagner A, Polizzi A, Lasserre F, Régnier M, Marmugi A, et al. Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling. PLoS ONE. 2017;12:e0181393 pubmed publisher
    ..We were particularly interested in addressing the contribution of Liver X Receptors (LXR) in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy ..
  9. Unsworth A, Bye A, Tannetta D, Desborough M, Kriek N, Sage T, et al. Farnesoid X Receptor and Liver X Receptor Ligands Initiate Formation of Coated Platelets. Arterioscler Thromb Vasc Biol. 2017;37:1482-1493 pubmed publisher
    The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists...

More Information

Publications41

  1. Kanaki M, Tiniakou I, Thymiakou E, Kardassis D. Physical and functional interactions between nuclear receptor LXR? and the forkhead box transcription factor FOXA2 regulate the response of the human lipoprotein lipase gene to oxysterols in hepatic cells. Biochim Biophys Acta Gene Regul Mech. 2017;1860:848-860 pubmed publisher
    ..in the liver are low but they can be strongly induced by a high cholesterol diet or by synthetic ligands of Liver X Receptors (LXRs). However, the mechanism by which LXRs activate the human LPL gene is unknown...
  2. McDonald G, Deepak S, Miguel L, Hall C, Isenberg D, Magee A, et al. Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients. J Clin Invest. 2014;124:712-24 pubmed publisher
    ..Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE. ..
  3. Nanduri R, Bhutani I, Somavarapu A, Mahajan S, Parkesh R, Gupta P. ONRLDB--manually curated database of experimentally validated ligands for orphan nuclear receptors: insights into new drug discovery. Database (Oxford). 2015;2015: pubmed publisher
    ..As demonstrated, ONRLDB is designed to allow selection of ligands based on various properties and for designing novel ligands or to improve the existing ones. Database URL: http://www.onrldb.org/. ..
  4. Chen L, Zhang L, Xian G, Lv Y, Lin Y, Wang Y. 25-Hydroxycholesterol promotes migration and invasion of lung adenocarcinoma cells. Biochem Biophys Res Commun. 2017;484:857-863 pubmed publisher
  5. Carbonnelle D, Luu T, Chaillou C, Huvelin J, Bard J, Nazih H. LXR Activation Down-regulates Lipid Raft Markers FLOT2 and DHHC5 in MCF-7 Breast Cancer Cells. Anticancer Res. 2017;37:4067-4073 pubmed
    ..LXR stimulation also reduces Akt phosphorylation and its localization at the plasma membrane. We showed, for the first time, that LXR regulates transcription of specific proteins of lipid rafts in a breast cancer model. ..
  6. Gatticchi L, Cerra B, Scarpelli P, Macchioni L, Sebastiani B, Gioiello A, et al. Selected cholesterol biosynthesis inhibitors produce accumulation of the intermediate FF-MAS that targets nucleus and activates LXR? in HepG2 cells. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862:842-852 pubmed publisher
    ..Moreover, a fluorescent ester derivative of FF-MAS localized in nuclear lipid droplets, suggesting a role for these organelles in the storage of signaling lipids interacting with nuclear partners. ..
  7. Yi M, Shin J, Lee S. Expression of CYP4V2 in human THP1 macrophages and its transcriptional regulation by peroxisome proliferator-activated receptor gamma. Toxicol Appl Pharmacol. 2017;330:100-106 pubmed publisher
    ..Further study is required to understand the role of CYP4V2 with regard to fat accumulation in the activated macrophage and atherosclerotic plaque development. ..
  8. Herold M, Breuer J, Hucke S, Knolle P, Schwab N, Wiendl H, et al. Liver X receptor activation promotes differentiation of regulatory T cells. PLoS ONE. 2017;12:e0184985 pubmed publisher
    ..Our data thus point towards a dual role of LXR-mediated control of inflammation by suppression of pro-inflammatory T cells and reciprocal induction of regulatory T cells. ..
  9. Leitch A, Probert P, Shayman J, Meyer S, Kass G, Wright M. B-13 progenitor-derived hepatocytes (B-13/H cells) model lipid dysregulation in response to drugs and chemicals. Toxicology. 2017;386:120-132 pubmed publisher
  10. Rong S, Cortés V, Rashid S, Anderson N, McDonald J, Liang G, et al. Expression of SREBP-1c Requires SREBP-2-mediated Generation of a Sterol Ligand for LXR in Livers of Mice. elife. 2017;6: pubmed publisher
    ..These studies demonstrate that cholesterol and FA synthesis in hepatocytes are coupled and that flux through the cholesterol biosynthetic pathway is required for the maximal SREBP-1c expression and high rates of FA synthesis. ..
  11. Sakane Y, Kanamoto N, Yamauchi I, Tagami T, Morita Y, Miura M, et al. Regulation of type 1 iodothyronine deiodinase by LXR?. PLoS ONE. 2017;12:e0179213 pubmed publisher
  12. Jeon J, Nam J, Kim H, Park Y, Bae S, Suh C. Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with systemic lupus erythematosus in Koreans. Arthritis Res Ther. 2014;16:R112 pubmed publisher
    b>Liver X receptors are established sensors of lipid and cholesterol homeostasis. Recent studies have reported that these receptors are involved in the regulation of inflammation and immune responses...
  13. Kim G, Oh G, Yoon J, Lee G, Lee K, Kim S. Hepatic TRAP80 selectively regulates lipogenic activity of liver X receptor. J Clin Invest. 2015;125:183-93 pubmed publisher
    ..Moreover, targeting the interaction between TRAP80 and LXR should facilitate the development of potential LXR agonists that effectively prevent atherosclerosis. ..
  14. Doran A, Ozcan L, Cai B, Zheng Z, Fredman G, Rymond C, et al. CAMKII? suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis. J Clin Invest. 2017;127:4075-4089 pubmed publisher
    ..These findings identify a macrophage CaMKII?/ATF6/LXR?/MerTK pathway as a key factor in the development of necrotic atherosclerotic plaques. ..
  15. Kim S, Kim J, Kim Y, Kim J, Park S. Nutritional regulation of renal lipogenic factor expression in mice: comparison to regulation in the liver and skeletal muscle. Am J Physiol Renal Physiol. 2017;313:F887-F898 pubmed publisher
    ..LXR is involved in the renal expression of lipogenic enzymes, and ChREBP may mediate the response. ..
  16. Lin E, Karakasheva T, Lee D, Lee J, Long Q, Bass A, et al. Comparative transcriptomes of adenocarcinomas and squamous cell carcinomas reveal molecular similarities that span classical anatomic boundaries. PLoS Genet. 2017;13:e1006938 pubmed publisher
    ..All data sets from our analysis are available as a resource for further investigation...
  17. Endo Umeda K, Aoyama A, Shimizu M, Ishikawa M, Hashimoto Y, Yamada S, et al. 1?-Hydroxy derivatives of 7-dehydrocholesterol are selective liver X receptor modulators. J Steroid Biochem Mol Biol. 2017;172:136-148 pubmed publisher
    ..These oxysterols have potential as LXR-targeted therapeutics for inflammatory disease. ..
  18. Athithan V, Srikumar K. 28-Homocastasterone down regulates blood glucose, cholesterol, triglycerides, SREBP1c and activates LxR expression in normal & diabetic male rat. Chem Biol Interact. 2017;277:8-20 pubmed publisher
    ..Western blots of marker protein, PCR amplicons of marker mRNA expressions and In Silico studies suggested that 28-HCeffect is being mediated through LxR molecular operatives in the rat cell. ..
  19. Bobin Dubigeon C, Chauvin A, Brillaud Meflah V, Boiffard F, Joalland M, Bard J. Liver X Receptor (LXR)-regulated Genes of Cholesterol Trafficking and Breast Cancer Severity. Anticancer Res. 2017;37:5495-5498 pubmed
    ..Liver X receptor [LXR; nuclear receptor subfamily 1, group H, member 2 (NR1H2, alias LXRB)] can inhibit proliferation and induce apoptosis of cancer cells. Its relationship with disease severity is not known...
  20. Amorim R, Daher I, Arcangelo F, Bellini M, Orcini W, Sarria G, et al. Short-term effects of green tea chronotherapy on the metabolic homeostasis of mice on different diets. Genet Mol Res. 2017;16: pubmed publisher
    ..The time at which green tea was consumed and the type of diet both influenced LXR?? nuclear receptor expression, as well as the expression of fibrillarin in the liver and ovaries, although this influence was tissue specific. ..
  21. Jeske J, Bitter A, Thasler W, Weiss T, Schwab M, Burk O. Ligand-dependent and -independent regulation of human hepatic sphingomyelin phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk with liver X receptor. Biochem Pharmacol. 2017;136:122-135 pubmed publisher
  22. Olivier M, BottG R, Frisdal E, Nowick M, Plengpanich W, Desmarchelier C, et al. ABCG1 is involved in vitamin E efflux. Biochim Biophys Acta. 2014;1841:1741-51 pubmed
    ..Overall, the present study reveals for the first time that ABCG1 is involved in cellular vitamin E efflux. ..
  23. Zhang Y, Wang L, Zhang J, Li Y, He Q, Li H, et al. Probiotic Lactobacillus casei Zhang ameliorates high-fructose-induced impaired glucose tolerance in hyperinsulinemia rats. Eur J Nutr. 2014;53:221-32 pubmed
    ..fragilis enriched vitamin K2-dependent osteocalcin mechanism in which AdipoR2, LXR-? and PPAR-? signaling were involved. ..
  24. Maczewsky J, Sikimic J, Bauer C, Krippeit Drews P, Wolke C, Lendeckel U, et al. The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting Mitochondrial Metabolism. Endocrinology. 2017;158:2145-2154 pubmed publisher
    ..This observation questions the chronic use of T0901317 and limits the interpretation of results obtained under these experimental conditions. ..
  25. Nikolova V, Papacleovoulou G, Bellafante E, Borges Manna L, Jansen E, Baron S, et al. Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis. Am J Physiol Endocrinol Metab. 2017;313:E463-E472 pubmed publisher
    ..b>Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the ..
  26. Marinozzi M, Castro Navas F, Maggioni D, Carosati E, Bocci G, Carloncelli M, et al. Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists. J Med Chem. 2017;60:6548-6562 pubmed publisher
    ..51 ?M). Interestingly, 13, 19, 20, and 25 showed to be LXR target gene-selective modulators, by strongly inducing the expression of ABCA1, while poorly or not activating the lipogenic genes SREBP1 and SCD1 or FASN, respectively. ..
  27. Li Z, Martin M, Zhang J, Huang H, Bai L, Zhang J, et al. Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility. Circulation. 2017;136:1315-1330 pubmed publisher
    ..KLF4 transactivates Ch25h and LXR, thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility. ..
  28. Suzuki M, Takeda S, Teraoka Nishitani N, Yamagata A, Tanaka T, Sasaki M, et al. Cadmium-induced malignant transformation of rat liver cells: Potential key role and regulatory mechanism of altered apolipoprotein E expression in enhanced invasiveness. Toxicology. 2017;382:16-23 pubmed publisher
    ..Together, the current results suggest that the cadmium-mediated enhanced cell invasion is linked to down-regulation of ApoE during malignant transformation these liver cells. ..
  29. Fond A, Lee C, Schulman I, Kiss R, Ravichandran K. Apoptotic cells trigger a membrane-initiated pathway to increase ABCA1. J Clin Invest. 2015;125:2748-58 pubmed publisher
    ..Collectively, these data identify a membrane-initiated pathway that is triggered by apoptotic cells to enhance ABCA1 within engulfing phagocytes and with functional consequences in vivo. ..
  30. Ji Q, Zhao Y, Yuan A, Pu J, He B. Deficiency of liver-X-receptor-? reduces glucose uptake and worsens post-myocardial infarction remodeling. Biochem Biophys Res Commun. 2017;488:489-495 pubmed publisher
    ..This study demonstrated that deficiency of LXR? decreased glucose uptake after MI, resulting in a metabolic shift that suppressed glucose metabolism, which was in association with adverse cardiac remodeling. ..
  31. Monzel J, Budde T, Meyer zu Schwabedissen H, Schwebe M, Bien Möller S, Lutjohann D, et al. Doxorubicin enhances oxysterol levels resulting in a LXR-mediated upregulation of cardiac cholesterol transporters. Biochem Pharmacol. 2017;144:108-119 pubmed publisher
    ..In this context, the cytotoxic effects of oxysterols and their impact on cardiac gene expression should be considered as an important factor in doxorubicin-induced cardiotoxicity. ..
  32. Rong X, Wang B, Palladino E, de Aguiar Vallim T, Ford D, Tontonoz P. ER phospholipid composition modulates lipogenesis during feeding and in obesity. J Clin Invest. 2017;127:3640-3651 pubmed publisher
    ..Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability. ..