Physical inactivity decreases whole body glutamine turnover independently from changes in proteolysis

Glutamine synthesis and utilization are strictly linked to energy metabolism and physical activity. To investigate the interaction between bed rest and moderate energy restriction on whole body glutamine kinetics in healthy volunteers, we performed a four-period study in which each subject randomly underwent a bed rest or ambulatory 14 day period both in eucaloric or hypocaloric (-20% of energy requirement) conditions. Glutamine kinetics were measured by l-[5-(15)N]glutamine and l-[1-(13)C]leucine primed continuous infusions in the postabsorptive state and during a 3 h infusion of a glutamine-free amino acid mixture (0.13 g amino acids (kg lean body mass (LBM))(-1) h(-1)). Bed rest decreased glutamine de novo synthesis in the postabsorptive state both in eucaloric (from 4.17 +/- 0.14 to 3.56 +/- 0.13 micromol (kg LBM)(-1) min(-1); P < 0.001) and in hypocaloric (from 3.79 +/- 0.19 to 3.49 +/- 0.14 micromol (kg LBM)(-1) min(-1); P < 0.001) conditions, independently of changes in whole body proteolysis. Bed rest did not affect glutamine clearance. We failed to detect either significant effects of energy intake or energy x activity interactions on glutamine kinetics. Bed rest significantly decreased postabsorptive plasma glutamine concentrations (P < 0.05). Amino acid infusion increased glutamine de novo synthesis rate and plasma glutamine concentrations in all conditions, without significant effects of bed rest or energy levels. We conclude that inactivity is associated with decreased whole body glutamine availability due to down-regulated de novo synthesis.