<br>营养补充剂L-α甘油磷酸胆碱促进动脉粥样硬化,International Journal of Molecular Sciences

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营养补充剂L-α甘油磷酸胆碱促进动脉粥样硬化
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2021-12-15 , DOI: 10.3390/ijms222413477
Zeneng Wang _{1,

2} , Jennie Hazen ₁ , Xun Jia ₁ , Elin Org ₃ , Yongzhong Zhao ₁ , Lucas J Osborn _{1,

2} , Nisreen Nimer ₁ , Jennifer Buffa ₁ , Miranda K Culley ₁ , Daniel Krajcik ₁ , Bert-Jan H van den Born ₄ , Koos Zwinderman ₄ , Bruce S Levison ₁ , Max Nieuwdorp ₄ , Aldons J Lusis ₅ , Joseph A DiDonato _{1,

2} , Stanley L Hazen _{1,

2,

6}

Affiliation

L -α 甘油磷酸胆碱 (GPC) 是一种营养补充剂，已被证明可以改善神经功能。然而，一项新的研究表明，补充 GPC 会增加中风风险，因此其潜在的副作用值得进一步研究。在这里，我们发现 GPC 促进高脂血症Apoe ^−/−小鼠的动脉粥样硬化。 GPC 可代谢为三甲胺 N-氧化物，这是一种促动脉粥样硬化剂，这表明所观察到的动脉粥样硬化进展背后存在潜在的分子机制。根据 16S rRNA 基因测序确定，GPC 补充剂改变了肠道微生物群落结构，其特征是副拟杆菌、瘤胃球菌和拟杆菌丰度增加，而阿克曼氏菌、乳杆菌和罗斯伯利亚丰度减少。这些数据与 GPC 喂养的小鼠粪便和盲肠短链脂肪酸的减少一致。此外，我们通过 qPCR 发现补充 GPC 会导致编码胆碱三甲胺裂解酶 ( cutC ) 的细菌的相对丰度增加。对宿主炎症信号传导的研究表明，补充 GPC 会增加人冠状动脉内皮细胞中促炎效应子 CXCL13 和 TIMP-1 的表达，并激活 NF-κB 和 MAPK 信号通路。最后，对小鼠血浆的靶向和非靶向代谢组学分析揭示了与 GPC 补充剂和动脉粥样硬化相关的其他代谢物。总之，我们的结果表明 GPC 通过多种机制促进动脉粥样硬化，在使用 GPC 作为营养补充剂时应谨慎。

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The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis

L-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC supplementation increases incident stroke risk thus its potential adverse effects warrant further investigation. Here we show that GPC promotes atherosclerosis in hyperlipidemic Apoe^−/− mice. GPC can be metabolized to trimethylamine N-oxide, a pro-atherogenic agent, suggesting a potential molecular mechanism underlying the observed atherosclerosis progression. GPC supplementation shifted the gut microbial community structure, characterized by increased abundance of Parabacteroides, Ruminococcus, and Bacteroides and decreased abundance of Akkermansia, Lactobacillus, and Roseburia, as determined by 16S rRNA gene sequencing. These data are consistent with a reduction in fecal and cecal short chain fatty acids in GPC-fed mice. Additionally, we found that GPC supplementation led to an increased relative abundance of choline trimethylamine lyase (cutC)-encoding bacteria via qPCR. Interrogation of host inflammatory signaling showed that GPC supplementation increased expression of the proinflammatory effectors CXCL13 and TIMP-1 and activated NF-κB and MAPK signaling pathways in human coronary artery endothelial cells. Finally, targeted and untargeted metabolomic analysis of murine plasma revealed additional metabolites associated with GPC supplementation and atherosclerosis. In summary, our results show GPC promotes atherosclerosis through multiple mechanisms and that caution should be applied when using GPC as a nutritional supplement.

更新日期：2021-12-15

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