Bile acid promotes liver regeneration via farnesoid X receptor signaling pathways in rats

Ding,Long; Yang,Yu; Qu,Yikun; Yang,Ting; Wang,Kaifeng; Liu,Weixin; Xia,Weibin

doi:10.3892/mmr.2015.3270

Bile acid promotes liver regeneration via farnesoid X receptor signaling pathways in rats

Authors:
- Long Ding
- Yu Yang
- Yikun Qu
- Ting Yang
- Kaifeng Wang
- Weixin Liu
- Weibin Xia
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Affiliations: The Second Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Department of Topographical Anatomy, College of Basic Medical Sciences, Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Department of Vascular Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China
Published online on: January 29, 2015 https://doi.org/10.3892/mmr.2015.3270
Pages: 4431-4437

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Abstract

Bile acids, which are synthesized from cholesterol in the hepatocytes of the liver, are amphipathic molecules with a steroid backbone. Studies have shown that bile acid exhibits important effects on liver regeneration. However, the mechanism underlying these effects remains unclear. The aim of the present study was to investigate the effect of bile acid and the farnesoid X receptor (FXR) on hepatic regeneration and lipid metabolism. Rats were fed with 0.2% bile acid or glucose for 7 days and then subjected to a 50 or 70% hepatectomy. Hepatic regeneration rate, serum and liver levels of bile acid, and expression of FXR and Caveolin‑1, were detected at 24, 48 or 72 h following hepatectomy. The expression of proliferating cell nuclear antigen (PCNA) in the liver was measured using immunohistochemistry at the end of the study. Hepatocytes isolated from rats were treated with bile acid, glucose, FXR agonist and FXR antagonist, separately or in combination. Lipid metabolism, the expression of members of the FXR signaling pathway and energy metabolism‑related factors were measured using ELISA kits or western blotting. Bile acid significantly increased the hepatic regeneration rate and the expression of FXR, Caveolin‑1 and PCNA. Levels of total cholesterol and high density lipoprotein were increased in bile acid‑ or FXR agonist‑treated hepatocytes in vitro. Levels of triglyceride, low density lipoprotein and free fatty acid were decreased. In addition, bile acid and FXR agonists increased the expression of bile salt export pump and small heterodimer partner, and downregulated the expression of apical sodium‑dependent bile acid transporter, Na+/taurocholate cotransporting polypeptide and cholesterol 7α‑hydroxylase. These results suggested that physiological concentrations of bile acid may promote liver regeneration via FXR signaling pathways, and may be associated with energy metabolism.

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