De novo glutamine synthesis induced by corticosteroids in vivo in rats is secondary to weight loss

Abstract

Introduction: Corticosteroid treatment affects muscle protein and glutamine metabolism. In the present study we aimed to clarify to what extent anorexia, weight loss and corticosteroids determine protein and glutamine metabolism in muscle.

Methods: The study was performed in Wistar rats (300-350 g, n = 40) given triamcinolone (0.25 mg/kg/day i.m.) treatment (CS group) for 14 days, sham treated free fed (FF group), sham treated pair fed (PF group) and sham treated pair weight (PW group). In vivo protein and glutamine turnover were measured using L-[2,6-3H]phenylalanine and L-[3,4-3H]glurtamine as tracer in a three compartment model across the hindquarter.

Results: Corticosteroid treatment decreased total body weight to a greater extent than can be explained by decreased food intake only, justifying the need for pair weight controls. Muscle weight loss was relatively greater in the corticosteroid treated rats than in the pair weight controls indicating specific corticosteroid induced changes in muscle protein metabolism. Pair weight rats increased muscle net protein breakdown rates from -5 +/- 3 nmol x 100 g body weight(-1) x min(-1) to -15 +/- 3 nmol x 100 g body weight(-1) x min(-1) (P < 0.05 vs FF). In the corticosteroid treated rats net protein breakdown rates increased to -22 +/- 4 nmol x 100 g body weight(-1) x min(-1) (P < 0.01 CS vs FF/PF) Net protein breakdown in corticosteroid treated rats was accompanied by increased glutamine efflux from the hindquarter (P < 0.05, CS vs FF/PF/PW). The latter could predominantly be explained by de novo synthesis. Furthermore, corticosteroid treatment induced a loss of plasma to free muscle glutamine gradient indicating down regulation of glutamine membrane transport rates into muscle. This effect was, however, similar in the pair weight control group and can thus be fully accounted for by the muscle weight loss.

Conclusion: Two weeks treatment with triamcinolone increases net in vivo protein breakdown of muscle directly and indirectly due to secondary weight loss and decreased food intake. The amino acid residues are used for glutamine de novo synthesis which is exported from muscle to visceral organs by down regulation of glutamine transport systems. These changes were in majority related to muscle weight loss.