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Hepatol Int. 2010 Aug 12;4(4):741-8. doi: 10.1007/s12072-010-9202-6.

Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease.

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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:

FXR; Human; Lipid metabolism; NAFLD

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