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



Título del documento: The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease
Revista: Annals of hepatology
Base de datos: PERIÓDICA
Número de sistema: 000411749
ISSN: 1665-2681
Autors: 1
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Institucions: 1Fundación Clínica Médica Sur, Unidad de Investigación de Hígado, México, Distrito Federal. México
2Instituto Nacional de Pediatría, Laboratorio de Bioquímica y Genética, México, Distrito Federal. México
3Universidad Nacional Autónoma de México, Facultad de Medicina, México, Distrito Federal. México
4Fundación Clínica Médica Sur, Departamento de Patología, México, Distrito Federal. México
Any:
Període: Jul-Ago
Volum: 14
Número: 4
Paginació: 487-493
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Analítico, descriptivo
Resumen en inglés 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, 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
Disciplines Medicina
Paraules clau: Gastroenterología,
Fisiopatología,
Hígado graso no alcohólico,
Receptores nucleares,
Función hepática
Keyword: Medicine,
Gastroenterology,
Physiopathology,
Non alcoholic fatty liver,
Nuclear receptors,
Liver function
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