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金丝桃苷对高脂饮食小鼠脂代谢调节作用的多组学分析

焦亚婷, 张雯姝, 潘珊珊, 谢明杰^*

辽宁师范大学生命科学学院，辽宁省生物技术与分子药物研发重点实验室，大连 116081

摘要

本研究旨在探讨金丝桃苷(hyperoside, Hyp)对高脂饮食小鼠脂代谢的调节作用。通过高脂饮食诱导建立高脂饮食小鼠模型，Hyp灌胃5周后用试剂盒测定小鼠血脂水平，用HE染色观察肝脏组织结构变化，用Illumina平台测量小鼠肠道菌群以及转录组的变化，用液相色谱-质谱联用法(liquid chromatography-mass spectrometry, LC-MS)测量非靶向代谢物水平。结果显示，Hyp能显著降低高脂饮食小鼠的血脂水平，使肝组织的外部形态和内部结构得到有效的恢复；Hyp能改变高脂饮食小鼠肠道菌群的物种组成，增加瘤胃球菌属等有益菌群的丰度，降低萨特氏菌属等有害菌群的丰度。多组学联合分析结果显示，Hyp喂食高脂饮食小鼠后，视黄酸对高脂饮食小鼠脂代谢的影响显著，而视黄酸含量的增加与肠道cyp1a2、ugt1a6b等基因表达呈显著负相关，与AF12丰度呈显著正相关，与unidentified_Desulfovibrionaceae丰度呈显著负相关。以上结果提示，Hyp可能通过调节肠道菌群AF12、unidentified_Desulfovibrionaceae等丰度和抑制cyp1a2、ugt1a6b等基因的表达，增加视黄酸的含量，调节高脂饮食小鼠的脂代谢。

关键词： 金丝桃苷; 肠道菌群; 转录组学; 代谢组学

Multi-omics analysis of regulating effects of hyperoside on lipid metabolism in high-fat diet mice

JIAO Ya-Ting, ZHANG Wen-Shu, PAN Shan-Shan, XIE Ming-Jie^*

School of Life Sciences, Liaoning Normal University, Key Laboratory of Biotechnology and Drug Discovery of Liaoning Province, Dalian 116081, China

Abstract

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.

Key words: hyperoside; intestinal flora; transcriptomics; metabolomics

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通讯作者：谢明杰　　E-mail: xmj1222@sina.com

引用本文：

焦亚婷, 张雯姝, 潘珊珊, 谢明杰. 金丝桃苷对高脂饮食小鼠脂代谢调节作用的多组学分析[J]. 生理学报 2022; 74 (6): 970-978.

JIAO Ya-Ting, ZHANG Wen-Shu, PAN Shan-Shan, XIE Ming-Jie. Multi-omics analysis of regulating effects of hyperoside on lipid metabolism in high-fat diet mice. Acta Physiol Sin 2022; 74 (6): 970-978 (in Chinese with English abstract).