Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism,Journal of Advanced Research

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Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2021-06-08 , DOI: 10.1016/j.jare.2021.06.001
Songsong Wang ₁ , Feiya Sheng ₁ , Liang Zou ₂ , Jianbo Xiao _{3,

4} , Peng Li ₁

Affiliation

Introduction

Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic total cholesterol (TC) and total triglyceride (TG) accumulation. In our previous study, we found that rats treated with hyperoside became resistant to hepatic lipid accumulation.

Objectives

The present study aims to investigate the possible mechanisms responsible for the inhibitory effects of hyperoside on the lipid accumulation in the liver tissues of the NAFLD rats.

Methods

Label-free proteomics and metabolomics targeting at bile acid (BA) metabolism were applied to disclose the mechanisms for hyperoside reducing hepatic lipid accumulation among the NAFLD rats.

Results

In response to hyperoside treatment, several proteins related to the fatty acid degradation pathway, cholesterol metabolism pathway, and bile secretion pathway were altered, including ECI1, Acnat2, ApoE, and BSEP, etc. The expression of nuclear receptors (NRs), including farnesoid X receptor (FXR) and liver X receptor α (LXRα), were increased in hyperoside-treated rats’ liver tissue, accompanied by decreased protein expression of catalyzing enzymes in the hepatic de novo lipogenesis and increased protein level of enzymes in the classical and alternative BA synthetic pathway. Liver conjugated BAs were less toxic and more hydrophilic than unconjugated BAs. The BA-targeted metabolomics suggest that hyperoside could decrease the levels of liver unconjugated BAs and increase the levels of liver conjugated BAs.

Conclusions

Taken together, the results suggest that hyperoside could improve the condition of NAFLD by regulating the cholesterol metabolism as well as BAs metabolism and excretion. These findings contribute to understanding the mechanisms by which hyperoside lowers the cholesterol and triglyceride in NAFLD rats.

中文翻译：

金丝桃苷通过胆固醇代谢和胆汁酸代谢减轻大鼠非酒精性脂肪肝

介绍

非酒精性脂肪性肝病 (NAFLD) 是由于肝脏总胆固醇 (TC) 和总甘油三酯 (TG) 积累增加所致。在我们之前的研究中，我们发现用金丝桃苷治疗的大鼠对肝脏脂质积累产生了抵抗力。

目标

本研究旨在探讨金丝桃苷抑制NAFLD大鼠肝组织脂质蓄积的可能机制。

方法

应用针对胆汁酸 (BA) 代谢的无标记蛋白质组学和代谢组学来揭示金丝桃苷减少 NAFLD 大鼠肝脏脂质积累的机制。

结果

金丝桃苷治疗后，与脂肪酸降解途径、胆固醇代谢途径和胆汁分泌途径相关的几种蛋白质发生了改变，包括 ECI1、Acnat2、ApoE 和 BSEP 等。核受体 (NRs) 的表达，包括法尼醇X 受体 (FXR) 和肝脏 X 受体 α (LXRα) 在金丝桃苷处理的大鼠肝组织中增加，伴随着肝脏从头脂肪生成中催化酶的蛋白质表达降低以及经典和替代中酶的蛋白质水平增加BA合成途径。肝脏结合的 BA 比未结合的 BA 毒性更小，亲水性更强。BA靶向代谢组学表明金丝桃苷可以降低肝脏非结合BA的水平并增加肝脏结合BA的水平。