Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro

Abstract 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‐1β, IL‐1α, 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.