Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease
- 12 August 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Hepatology International
- Vol. 4 (4), 741-748
- https://doi.org/10.1007/s12072-010-9202-6
Abstract
The aim of this study was to explore the role of farnesoid X receptor (FXR) in liver lipid metabolism of non-alcoholic fatty liver disease (NAFLD) patients. In this study, pathology and clinical criteria confirmed NAFLD in patients. Fatty acid synthetase (FAS)-positive liver cells were visualized by laser scanning confocal microscopy. Levels of FXR, liver X receptor (LXR), sterol regulatory element binding protein 1C (SREBP-1C), and small heterodimer partner (SHP) proteins were detected by Western blot. FXR, LXR, and SHP mRNA levels were measured by real-time PCR. In patients with NAFLD, a significant positive relationship between the degree of hepatic steatosis and serum triglycerides and cholesterol (correlation coefficient > 0.5, P < 0.05) was seen. The NAFLD patients had more FAS protein in liver, which suggests that there could have been more of fatty acid synthesis in hepatic cells (P < 0.05). The levels of FXR protein and mRNA were decreased in patients with NAFLD (P < 0.05), while those of LXR and SREBP-1C were increased (P < 0.05). The levels of SREBP-1C positively correlated with the degree of hepatic steatosis. There were no differences between the levels of SHP protein and mRNA both in NAFLD patients and normal controls (P > 0.05). Our data showed that the decreased expression of hepatic FXR is associated with an increased expression of LXR, SREBP-1C, and hepatic triglyceride synthesis; furthermore, increased SREBP-1C is associated with the degree of hepatic steatosis in the NAFLD patients.Keywords
This publication has 29 references indexed in Scilit:
- Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistanceBiochemical Society Transactions, 2008
- Significant correlations between severe fatty liver and risk factors for metabolic syndromeJournal of Gastroenterology and Hepatology, 2007
- A little orphan runs to fat: The orphan receptor small heterodimer partner as a key player in the regulation of hepatic lipid metabolismJournal of Hepatology, 2007
- Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liverJournal of Hepatology, 2007
- Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding modelJournal of Hepatology, 2006
- New insights in the pathogenesis of non-alcoholic fatty liver diseaseCurrent Opinion in Lipidology, 2006
- Ins and Outs Modulating Hepatic Triglyceride and Development of Nonalcoholic Fatty Liver DiseaseGastroenterology, 2006
- Structure and function of steroid receptor AF1 transactivation domains: induction of active conformationsBiochemical Journal, 2005
- The Farnesoid X ReceptorArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Holding the line on hepatic fatCell Metabolism, 2005