1. Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism
- Author
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Songsong Wang, Peng Li, Liang Zou, Jianbo Xiao, and Feiya Sheng
- Subjects
0301 basic medicine ,Apolipoprotein E ,SREBPs, sterol regulatory element binding proteins ,SREBP2, sterol regulatory element-binding protein 2 ,SHP, small heterodimer partner ,chemistry.chemical_compound ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,LXRα, liver X receptor α ,VLDL, very low-density lipoprotein ,Multidisciplinary ,TG, triglyceride ,Bile acid ,Chemistry ,Fatty liver ,FGF15/19, fibroblast growth factor 15/19 ,Cholesterol ,WB, Western blot ,ACC, Acetyl-CoA carboxylase ,030220 oncology & carcinogenesis ,Lipogenesis ,Quercetin ,NAFLD, non-alcoholic fatty liver disease ,medicine.medical_specialty ,Bile acid metabolism ,SDS, sodium dodecyl sulfate ,TGR5, Takeda G-protein-coupled receptor 5 ,medicine.drug_class ,Hyperoside ,LC-MS, the combination of high-performance liquid chromatography and mass spectrometry ,Article ,Bile Acids and Salts ,pACC, phosphorylated ACC ,03 medical and health sciences ,Label-free proteomics ,FXR, farnesoid X receptor ,CYP27A1, sterol 27-hydroxylase ,NAFLD ,Internal medicine ,medicine ,Animals ,Cholesterol metabolism ,Liver X receptor ,ComputingMethodologies_COMPUTERGRAPHICS ,BAs, bile acids ,SREBP1, sterol regulatory element-binding protein 1 ,Targeted metabolomics ,Lipid Metabolism ,CYP7A1, cholesterol 7α-hydroxylase ,medicine.disease ,Rats ,TC, total cholesterol ,QC, quality control ,AMPK, AMP-activated protein kinase ,030104 developmental biology ,Endocrinology ,PMSF, phenylmethylsulfonyl fluoride ,Apo, apolipoprotein ,BSH, bile salt hydrolase ,Farnesoid X receptor - Abstract
Graphical abstract, 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.
- Published
- 2021