¹H-NMR metabolomics identifies significant changes in hypermetabolism after glutamine administration in burned rats

Glutamine is an important amino acid that plays a crucial role in nutritional therapy for patients with burns, but its effects on post-burn metabolism and the underlying mechanisms are unclear. In this study, ¹H nuclear magnetic resonance spectroscopy (¹H-NMR) was used to examine the effects of glutamine on plasma metabolites in burned rats and to explore the underlying mechanisms. After burn injury, the rats exhibited significant increases in resting energy expenditure (REE) and hypercatabolism, and anabolism was inhibited. The levels of metabolites that reflect the proteolysis of skeletal muscle, such as alanine, histidine, leucine, valine, 3-methylhistidine and creatine, were significantly increased. In addition, the burned rats exhibited energy synthesis dysfunction, as evidenced by a decrease in the ATP concentration and increased levels of lactic acid. Notably, the concentration of α-ketoisovalerate, which reflects the function of the mitochondrial membrane, was significantly increased, suggesting an impairment in mitochondrial function and inhibition of oxidative phosphorylation. Glutamine administration significantly alleviated post-burn hypermetabolism and inhibited proteolysis in skeletal muscle. Consequently, the levels of glutamine metabolites, such as glutamic acid and α-ketoglutarate, along with ATP synthesis were significantly increased, whereas alanine, leucine, 3-methylhistidine and lactic acid were significantly depleted. Furthermore, after glutamine administration, the synthesis of reductive compounds was increased, leading to significantly increased levels of reduced glutathione and NADPH. This process may be an important mechanism by which glutamine alleviates oxidative stress, promotes ATP synthesis, and reduces hypermetabolism after burn.