title: The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Patients with non-alcoholic steatohepatitis (NASH) have increased plasmatic and hepatic concentrations of bile acids (BA), suggesting that they can be associated with the progression of the disease. Hepatic nuclear receptors are known to modulate genes controlling BA metabolism; thus, in this work we aimed to compare the expression of liver nuclear receptors -farnesoid X (FXR), small heterodimer partner (SHP) and liver X alpha (LXRα) receptors- and BA transporters -sodium+/taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP)- in liver biopsy samples of patients with simple steatosis (SS) and NASH.
  
  
  METHODS
  Forty patients with biopsy-proven NALFD were enrolled between 2009 and 2012; liver biopsies were classified as SS (N = 20) or NASH (N = 20) according to the NAFLD activity score. Gene expression of nuclear FXR, LXRα, SHP, NTCP and BSEP was analyzed by real-time reverse transcription polymerase chain reaction and protein level was quantified by western blot.
  
  
  RESULTS
  Gene expression of FXR, SHP, NTCP and BSEP was significantly up-regulated in the NASH group in comparison with SS patients (P < 0.05). In contrast, protein level for FXR, SHP and NTCP was decreased in the NASH patients vs. the SS group (P < 0.05). Gene and protein profile of LXRα did not show differences between groups.
  
  
  CONCLUSIONS
  The results suggest that liver nuclear receptors (FXR and SHP) and BA transporters (NTCP and BSEP) are associated with the progression of NAFLD.
authors.affiliation: Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Aguilar-Olivos
authors.affiliation: Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Carrillo-Córdova
authors.affiliation: Biochemistry and Genetics Lab, National Institute of Pediatrics, Ministry of Health, Mexico City, Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: Oria-Hernández
authors.affiliation: Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Vicente
authors.initials: V
authors.lastname: Sánchez-Valle
authors.affiliation: Public Health Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ponciano-Rodríguez
authors.affiliation: Pathology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramírez-Jaramillo
authors.affiliation: Pathology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Fredy
authors.initials: F
authors.lastname: Chablé-Montero
authors.affiliation: Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Chávez-Tapia
authors.affiliation: Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Misael
authors.initials: M
authors.lastname: Uribe
authors.affiliation: Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
authors.forename: Nahum
authors.initials: N
authors.lastname: Méndez-Sánchez
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000235:genetics; D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000032:analysis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D064486:Solute Carrier Family 12, Member 3 / Q000032:analysis / Q000235:genetics; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D064486:Solute Carrier Family 12, Member 3; D000099150:Receptor, Farnesoid X-Activated; C093491:ABCB11 protein, human; C000605213:NR1H3 protein, human; C578874:SLC12A3 protein, human; C099713:nuclear receptor subfamily 0, group B, member 2