Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro

This study aimed to clarify the role of glutamine in atherosclerosis and its participating mechanism. Forty C57BL/6J mice were divided into wild control (wild Con), ApoE(-/-) control (ApoE(-/-) Con), glutamine + ApoE(-/-)control (Glut + ApoE(-/-) Con), ApoE(-/-) high fat diet (ApoE(-/-) HFD), and glutamine + ApoE(-/-) HFD (Glut + ApoE(-/-) HFD) groups. The degree of atherosclerosis, western blotting, and multiomics were detected at 18 weeks. An in vitro study was also performed. Glutamine treatment significantly decreased the degree of aortic atherosclerosis (p = 0.03). O-GlcNAcylation (O-GlcNAc), IL-1 beta, IL-1 alpha, and pyruvate kinase M2 (PKM2) in the ApoE(-/-) HFD group were significantly higher than those in the ApoE(-/-) Con group (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05), and aggravated by O-GlcNA transferase (OGT) overexpression in the in vitro study (p < 0.05). Multiomics showed that the ApoE(-/-) HFD group had higher levels of oxidative stress regulatory molecules (guanine deaminase [GUAD], xanthine dehydrogenase [XDH]), proinflammatory regulatory molecules (myristic acid and myristoleic acid), and stress granules regulatory molecules (caprin-1 and deoxyribose-phosphate aldolase [DERA]) (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05). We conclude that glutamine supplementation might alleviate atherosclerosis through downregulation of O-GlcNAc, glycolysis, oxidative stress, and proinflammatory pathway.