The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease

• Published in: Annals of hepatology Vol. 14; no. 4; pp. 487 - 493
• Main Authors: Aguilar-Olivos, Nancy E, Carrillo-Córdova, Daniel, Oria-Hernández, Jesús, Sánchez-Valle, Vicente, Ponciano-Rodríguez, Guadalupe, Ramírez-Jaramillo, Manuel, Chablé-Montero, Fredy, Chávez-Tapia, Norberto C, Uribe, Misael, Méndez-Sánchez, Nahum, MD, MSc, PhD, FACG, AGAF
• Format: Journal Article
• Language: English
• Published: Mexico Elsevier 01.07.2015
• Subjects: Adult; Association; ATP Binding Cassette Subfamily B Member 11; ATP-Binding Cassette Transporters - analysis; ATP-Binding Cassette Transporters - genetics; Biopsy; Blotting, Western; Disease Progression; Fatty liver; Female; Gastroenterology and Hepatology; Gene Expression Profiling - methods; Humans; Liver - chemistry; Liver - pathology; Liver X Receptors; Male; Middle Aged; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - metabolism; Nuclear receptors; Orphan Nuclear Receptors - analysis; Orphan Nuclear Receptors - genetics; Real-Time Polymerase Chain Reaction; Receptors, Cytoplasmic and Nuclear - analysis; Receptors, Cytoplasmic and Nuclear - genetics; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Solute Carrier Family 12, Member 3 - analysis; Solute Carrier Family 12, Member 3 - genetics; Up-Regulation; Nuclear receptors; Fatty liver; Association
• ISSN: 1665-2681; 2659-5982
• DOI: 10.1016/S1665-2681(19)31170-6

AbstractBackground. 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. 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, LXRa, 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 LXRa 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.