title: Expression of liver X receptor correlates with intrahepatic inflammation and fibrosis in patients with nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Liver X receptor (LXR) is an oxysterol-activated nuclear receptor involved in the control of major metabolic pathways for cholesterol homeostasis and lipogenesis. Although the role of LXR in hepatic steatosis is well known, its correlation with intrahepatic inflammation and fibrosis has not been thoroughly studied. We investigated the association between LXRα, hepatic inflammation, and fibrosis, as well as its correlation with other intrahepatic lipid transporters in patients with nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  We evaluated clinical characteristics including sex, age, body mass index, and laboratory findings from 40 NAFLD and 16 control patients. Immunohistochemical staining was carried out on liver biopsy samples from all patients.
  
  
  RESULTS
  The positive rate of LXRα expression was 30 % in the control group, 50 % in the NAFLD group, and 97 % in NASH groups. LXRα expression was positively correlated with not only the amount of intrahepatic fat, but also with intrahepatic inflammation and hepatic fibrosis. LXRα expression showed positive correlation with intrahepatic expression of ABCG5/8, CD36, and SREBP-1c. The expression of ABCA1, ABCG5/8, SREBP-1c, and CD36 was higher in NAFLD than in controls and there was no further increase in the NASH group. NPC1L1 was abundant in human liver. Expression of NPC1L1 was negatively correlated with intrahepatic inflammation and LXRα intensity.
  
  
  CONCLUSIONS
  LXR expression correlated with the degree of hepatic fat deposition, as well as with hepatic inflammation and fibrosis in NAFLD patients. Our research suggests that LXR is an attractive target for treatment and regulation of hepatic inflammation and fibrosis.
authors.affiliation: Department of Internal Medicine, Eulji University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Bong
authors.initials: SB
authors.lastname: Ahn
authors.forename: Kiseok
authors.initials: K
authors.lastname: Jang
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Jun
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Lee
authors.forename: Kye Jung
authors.initials: KJ
authors.lastname: Shin
mesh_terms: D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism*; D000071518:Liver X Receptors; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D002784:Cholesterol
references.citation: Cell Metab. 2013 Jul 2;18(1):106-17
references.pmid: 23823481
references.citation: Nature. 1996 Oct 24;383(6602):728-31
references.pmid: 8878485
references.citation: J Hepatol. 2013 May;58(5):984-92
references.pmid: 23333450
references.citation: J Lipid Res. 2010 Nov;51(11):3135-44
references.pmid: 20699423
references.citation: Biotechniques. 2005 Dec;39(6):822, 824, 826
references.pmid: 16382898
references.citation: Prostate. 2011 Sep 15;71(13):1374-81
references.pmid: 21308718
references.citation: Hepatology. 2007 Jun;45(6):1366-74
references.pmid: 17476695
references.citation: Dig Dis Sci. 2012 Feb;57(2):390-8
references.pmid: 21948338
references.citation: Circulation. 2006 Jan 3;113(1):90-7
references.pmid: 16365197
references.citation: Nat Med. 2003 Feb;9(2):213-9
references.pmid: 12524534
references.citation: Expert Opin Ther Targets. 2011 Feb;15(2):219-32
references.pmid: 21204733
references.citation: Biochem Pharmacol. 2006 Feb 14;71(4):453-63
references.pmid: 16325781
references.citation: Annu Rev Cell Dev Biol. 2000;16:459-81
references.pmid: 11031244
references.citation: J Clin Invest. 2007 Jul;117(7):1968-78
references.pmid: 17571164
references.citation: Hepatology. 2005 Jun;41(6):1313-21
references.pmid: 15915461
references.citation: Gastroenterology. 2011 Mar;140(3):1052-62
references.pmid: 21134374
references.citation: Am J Physiol Endocrinol Metab. 2005 Nov;289(5):E829-38
references.pmid: 15941783
references.citation: J Lipid Res. 2008 Feb;49(2):464-72
references.pmid: 18007013
references.citation: Shock. 2006 Feb;25(2):141-6
references.pmid: 16525352
references.citation: FEBS Lett. 2010 Mar 5;584(5):1001-5
references.pmid: 20114046
references.citation: Gastroenterology. 2008 Feb;134(2):556-67
references.pmid: 18242221