Adverse effects of chronic intake of glutamine-supplemented diet on amino acid concentrations and protein metabolism in rat: Effect of short-term starvation

Abstract

Summary Background & aims Glutamine supplementation is recommended in severe illness, preterm infants, and athletes. However, the information about side effects of chronic intake of glutamine-supplemented diet is limited. Methods Male Wistar rats were fed with glutamine-supplemented diet (GlnD). The controls were fed by standard or high-protein diets. After three months, the effect of GlnD on amino acid concentration in body fluids and protein metabolism was examined in fed and in 24 h-fasted animals. Protein synthesis was examined by the “flooding method” using phenylalanine; proteolysis on the basis of chymotrypsin-like activity (CHTLA) of proteasome and cathepsin B and L activities; amino acid concentrations were estimated using HPLC. Student’s t -tests with Bonferroni correction were used for statistical analysis. Results In the blood of GlnD fed animals sacrificed in fed state we found higher concentrations of glutamine, urea, and histidine, and lower concentration of creatinine and of a number of amino acids than in controls. The main alterations in intracellular free amino acid concentration were increased concentration of glutamine, increased concentration of histidine in skeletal muscle, and decreased concentrations of glycine, serine, and threonine in several tissues. In GlnD fed animals we found enhanced amount and concentration of protein in the kidneys, decreased protein content in tibialis muscle, and enhanced CHTLA in soleus muscle. We did not find significant effect on protein synthesis in any tissue. Starvation of animals previously fed by GlnD led to a marked decrease in glutamine concentration and an increase in glycine, serine, and threonine in plasma and in most of examined tissues, and in more significant decrease in protein synthesis in the liver, jejunum, colon, and spleen than in animals fed before starvation by standard diet. Conclusions It is concluded that chronic intake of GlnD has negative effect on protein balance in skeletal muscle, significantly alters amino acid concentrations in plasma and tissues, and results in impaired response to starvation, particularly to the rapid development of glutamine deficiency in body fluids and impaired protein synthesis in visceral tissues.