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A combined transcriptomics and proteomics approach to reveal the mechanism of AEE relieving hyperlipidemia in ApoE-/- mice

文献类型： 外文期刊

作者： Lu, Xiao-Rong 1 ; Tao, Qi 1 ; Qin, Zhe 1 ; Liu, Xi -Wang 1 ; Li, Shi-Hong 1 ; Bai, Li-Xia 1 ; Ge, Wen-Bo 1 ; Liu, Ya-Xian 1 ; Li, Jian-Yong 1 ; Yang, Ya-Jun 1 ;

作者机构： 1.Chinese Acad Agr Sci, Lanzhou Inst Husb & Pharmaceut Sci, Key Lab New Anim Drug Gansu Prov, Key Lab Vet Pharmaceut Dev,Minist Agr & Rural Affa, Lanzhou 730050, Peoples R China

2.335 Jiangouyan, Lanzhou 730050, Peoples R China

关键词： Aspirin eugenol ester (AEE); Hyperlipidemia; Proteomics; Transcriptomics; ApoE -/; mice

期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：7.5； 五年影响因子：6.8 ）

ISSN： 0753-3322

年卷期： 2024 年 173 卷

页码：

收录情况： SCI

摘要： Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough. In this study, the mechanism and potential key pathways of AEE on improving hyperlipidemia in mice were investigated through the transcriptome and proteome study of ApoE-/- mice liver and the verification study on high-fat HepG2 cells. The results showed that AEE significantly decreased the serum TC and LDL-C levels of hyperlipidemia ApoE-/- mice, and significantly increased the enzyme activity of CYP7A1. After AEE intervention, the results of mice liver transcriptome and proteome showed that differential genes and proteins were enriched in lipid metabolismrelated pathways. The results of RT-qPCR showed that AEE significantly regulated the expression of genes related to lipid metabolism in mice liver tissue. AEE significantly upregulated the protein expression of CYP7A1 in hyperlipidemia ApoE-/- mice liver tissue. The results in vitro showed that AEE significantly decreased the levels of TC and TG, and improved lipid deposition in high-fat HepG2 cells. AEE significantly increased the expression of CYP7A1 protein in high-fat HepG2 cells. AEE regulates the expression of genes related to lipid metabolism in high-fat HepG2 cells, mainly by FXR-SHP-CYP7A1 and FGF19-TFEB-CYP7A1 pathways. To sum up, AEE can significantly improve the hyperlipidemia status of ApoE-/- mice and the lipid deposition of high-fat HepG2 cells, and its main pathway is probably the bile acid metabolism-related pathway centered on CYP7A1.

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