The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis

Int J Mol Sci. 2021 Dec 15;22(24):13477. doi: 10.3390/ijms222413477.ABSTRACTL-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 supplement...

Source: Atherosclerosis - December 24, 2021 Category: Cardiology Authors: Zeneng Wang Jennie Hazen Xun Jia Elin Org Yongzhong Zhao Lucas J Osborn Nisreen Nimer Jennifer Buffa Miranda K Culley Daniel Krajcik Bert-Jan H van den Born Koos Zwinderman Bruce S Levison Max Nieuwdorp Aldons J Lusis Joseph A DiDonato Stanley L Hazen Source Type: research