PMID- 26019035 OWN - NLM STAT- MEDLINE DCOM- 20160229 LR - 20190919 IS - 1665-2681 (Print) IS - 1665-2681 (Linking) VI - 14 IP - 4 DP - 2015 Jul-Aug TI - The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease. PG - 487-93 AB - 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 (LXRalpha) 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. MATERIAL AND 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, LXRalpha, 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 LXRalpha 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. FAU - Aguilar-Olivos, Nancy E AU - Aguilar-Olivos NE AD - Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Carrillo-Cordova, Daniel AU - Carrillo-Cordova D AD - Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Oria-Hernandez, Jesus AU - Oria-Hernandez J AD - Biochemistry and Genetics Lab, National Institute of Pediatrics, Ministry of Health, Mexico City, Mexico. FAU - Sanchez-Valle, Vicente AU - Sanchez-Valle V AD - Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Ponciano-Rodriguez, Guadalupe AU - Ponciano-Rodriguez G AD - Public Health Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico. FAU - Ramirez-Jaramillo, Manuel AU - Ramirez-Jaramillo M AD - Pathology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Chable-Montero, Fredy AU - Chable-Montero F AD - Pathology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Chavez-Tapia, Norberto C AU - Chavez-Tapia NC AD - Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Uribe, Misael AU - Uribe M AD - Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico. FAU - Mendez-Sanchez, Nahum AU - Mendez-Sanchez N AD - Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Mexico TA - Ann Hepatol JT - Annals of hepatology JID - 101155885 RN - 0 (ABCB11 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 11) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Liver X Receptors) RN - 0 (NR1H3 protein, human) RN - 0 (Orphan Nuclear Receptors) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (SLC12A3 protein, human) RN - 0 (Solute Carrier Family 12, Member 3) RN - 0 (nuclear receptor subfamily 0, group B, member 2) RN - 0C5V0MRU6P (farnesoid X-activated receptor) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 11 MH - ATP-Binding Cassette Transporters/*analysis/genetics MH - Adult MH - Biopsy MH - Blotting, Western MH - Disease Progression MH - Female MH - Gene Expression Profiling/methods MH - Humans MH - Liver/*chemistry/pathology MH - Liver X Receptors MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/diagnosis/genetics/*metabolism MH - Orphan Nuclear Receptors/*analysis/genetics MH - Real-Time Polymerase Chain Reaction MH - Receptors, Cytoplasmic and Nuclear/*analysis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Severity of Illness Index MH - Solute Carrier Family 12, Member 3/analysis/genetics MH - Up-Regulation EDAT- 2015/05/29 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/05/29 06:00 PHST- 2015/05/29 06:00 [entrez] PHST- 2015/05/29 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] AID - S1665-2681(19)31170-6 [pii] PST - ppublish SO - Ann Hepatol. 2015 Jul-Aug;14(4):487-93.