Eicosapentaenoic Acid-Enriched Phosphoethanolamine Plasmalogens Alleviated Atherosclerosis by Remodeling Gut Microbiota to Regulate Bile Acid Metabolism in LDLR-/- Mice
Eicosapentaenoic Acid-Enriched Phosphoethanolamine Plasmalogens Alleviated Atherosclerosis by Remodeling Gut Microbiota to Regulate Bile Acid Metabolism in LDLR-/- Mice
复制标题
富含二十碳五烯酸的磷酸乙醇胺缩醛磷脂通过重塑肠道微生物群来调节 LDLR-/- 小鼠的胆汁酸代谢，从而减轻动脉粥样硬化
DOI：
10.1021/acs.jafc.9b08296
复制
发表时间：
2020-05-13
影响因子：
6.1
通讯作者：
Wang, Yu-Ming
中科院分区：
文献类型：
--
作者：
Ding, Lin;Zhang, Ling-Yu;Wang, Yu-Ming
富含二十碳五烯酸（EPA）的磷酸乙醇胺缩醛磷脂（EPA-PlsEtns）可能在治疗后长时间保留在富含肠道微生物群的肠道中。它提醒我们，EPA-PlsEtns可能会影响肠道微生物群组成及其代谢产物，这已被确定为心血管疾病发展的一个促成因素。在本研究中，EPA-PlsEtn给药8周显著减少了低密度脂蛋白受体缺陷（LDLR-/-）小鼠的动脉粥样硬化病变面积。值得注意的是，与模型组相比，通过EPA-PlsEtns代替乙酯形式的EPA（EPA-EE）治疗，血清总胆固醇和低密度脂蛋白胆固醇水平分别显著降低了33.6%和38.2%。EPA-PlsEtn给药还使粪便中的总中性固醇和胆汁酸分别增加了92%和39%，而不是EPA-EE JPA-PlsEtn可能会影响肠道微生物群的丰度，从而导致胆汁酸谱的改变，这可能会通过增加由法尼醇X受体活化的抑制诱导的胆固醇7 α-羟化酶表达来进一步加速胆汁酸合成。
Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR-/-) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 alpha-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.