Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats

Abstract

Although glutamine status in the critically ill patient can be improved by nutritional means, the most effective way of effecting such supplementation has received little attention. We evaluated two different ways of supplementing clinical nutrition products with glutamine, either with free glutamine or by providing a glutamine-rich protein source, in acute glucocorticoid-treated (intraperitoneal dexamethasone, 120 mg/kg) rats. During the recovery period, the animals received isonitrogenous and isoenergetic diets containing either casein, mixed whey proteins with or without glutamine, or carob protein plus essential amino acids. Plasma and tissue amino acids and glutathione as well as tissue protein synthesis were measured. Dexamethasone treatment lowered weight gain, muscle glutamine, and muscle and jejunal protein synthetic rate. Muscle protein synthesis was increased (from 15.9% to 24.2%/d) only when glutamine was included in the diet as a free amino acid. This increase paralleled a rise in plasma glutamine. We speculate that glutamine provided in dietary protein is extensively metabolized by the splanchnic tissues and does not influence peripheral glutamine status to the same extent as glutamine provided in a free amino acid form. However, both forms of glutamine supplementation were equally effective in increasing protein synthesis in the jejunum (by 25%). This is likely the main benefit of glutamine supplementation of enteral nutrition formulas.

Introduction

Glutamine is a non-essential amino acid that acts not only as a precursor for protein synthesis but is an important intermediate in a large number of metabolic pathways. It is the most important substrate for ammoniagenesis in the kidney, is a precursor of the synthesis of purines and pyrimidines, and serves as a nitrogen transporter between various tissues. It appears to be of specific functional importance to proliferating cells, including those of the immune and intestinal mucosal systems.1

During hypercatabolic states, enterocytes and immune cells increase glutamine uptake. Although the rate of release of glutamine from skeletal muscle increases in starvation, acidosis, trauma, sepsis, and burns,2 circulating and skeletal muscle glutamine concentrations tend to fall, thereby indicating that the increased demands for glutamine are in excess of the individual’s capability for glutamine synthesis. Under these circumstances there are good reasons to propose that an exogenous supply of glutamine might be of benefit to both the gut and the immune system.3 In addition, glutamine supplementation may promote protein synthesis and inhibit protein catabolism in muscle.4, 5

It is well established that the administration of dexamethasone (DEX), a synthetic glucocorticoid, initiates a catabolic response. It has been argued that this response releases muscle amino acids for gluconeogenesis and the synthesis of acute-phase proteins by the liver.6 It includes an increased degradation and decreased synthesis of protein in several tissues.7, 8, 9 It has been shown that the gastrointestinal tract is more sensitive than skeletal muscle to the protein catabolic effects of corticosterone treatment.10 Specifically, the catabolic response was confined to the small intestine and not the jejunum. Burrin et al.11 have recently shown that DEX significantly inhibits small intestine growth via both increased degradation and decreased synthesis of protein. DEX is also a potent immunosuppressive agent capable of directly affecting the function and number of circulating lymphocytes, macrophages, and other immune cells. Moreover, intraperitoneal DEX administration (in similar doses to those used in the present study) resulted in significant suppression of lymphokine production and cell proliferation.12 Indeed, it has been used as a reversible model of immunosuppression.

The main objective of the present work was to study the efficacy of four diets differing in glutamine content and form in which glutamine was provided, on nutritional and functional recovery in animals treated with DEX. The protein sources were as follows: casein; mixed whey proteins; whey proteins plus glutamine; and carob proteins. Carob proteins were chosen as the protein-contained glutamine source because of their high content of glutamine (17 g/100 g protein) and their low potential antigenicity, compared to wheat gluten. Carob proteins were supplemented with essential amino acids to fullfil rat amino acid requirements.