Calorie restriction accelerates the catabolism of lean body mass during 2 wk of bed rest.

BACKGROUND: Muscle inactivity and low energy intake commonly occur in persons with acute or chronic disease, in astronauts during space flight, and during aging. OBJECTIVE: We used a crossover design to investigate the effects of the interactions of inactivity and calorie restriction on whole-body composition and protein kinetic regulation in 9 healthy volunteers. DESIGN: Lean body mass (LBM) was measured by using dual-energy X-ray absorptionmetry before and at the end of 14-d periods of bed rest (B) and controlled ambulation (A) in patients receiving eucaloric (E) or hypocaloric (H) (approximately 80% of total energy expenditure) diets. Whole-body leucine kinetics were determined at the end of the 4 study periods by using a standard stable-isotope technique in the postabsorptive state and during a 3-h infusion of a 0.13 g x kg LBM(-1) x h(-1) amino acid mixture. RESULTS: In the postabsorptive state, we found a significant (P = 0.04) bed rest x hypocaloric diet interaction for the rate of leucine oxidation, an index of net protein catabolism (A+E: 0.23 +/- 0.01; B+E: 25 +/- 0.01; A+H: 0.23 +/- 0.01; B+H: 0.28 +/- 0.01 micromol x min(-1) x kg LBM(-1)). Bed rest significantly (P < 0.01) decreased amino acid-mediated stimulation of nonoxidative leucine disappearance, an index of protein synthesis (A+E: 35 +/- 2%; B+E: 30 +/- 2%; A+H: 41 +/- 3%; B+H: 32 +/- 2%). B+H decreased LBM by 1.10 +/- 0.1 kg, which is significantly (P < 0.01) greater than the decrease seen with A+E, A+H, or B+E. CONCLUSION: Calorie restriction enhanced the catabolic response to inactivity by combining greater protein catabolism in the postabsorptive state with an impaired postprandial anabolic utilization of free amino acids.

Increased urinary excretion rates of serotonin and metabolites during bedrest.

Astronauts are often on a voluntarily reduced energy intake during space missions, possibly caused by a metabolic or emotional stress response with involvement of the central serotonergic system (SES). We investigated 24 h urinary excretion (24 h-E) of serotonin (5-HT) and 5-hydroxyindol acidic acid as indicators of the SES in healthy males under two different normocaloric conditions: normal physical activity (NPA) and -6 degree head-down-tilt (HDT). HDT or NPA were randomly arranged with a recovery period of 6 months in between. 24 h-E of hormones varied widely among individuals. Values were higher in HDT compared to NPA. Assuming that the 24 h-E values are, beside being indicators for alterations in the number and metabolism of platelets. Also indicators of central SES, HDT condition seems to activate central SES in a higher degree compared to NPA. Therefore, changes in central SES might be involved in the mechanisms associated with space flight or microgravity, including possible maladaptations such as voluntary undernutrition.

Short-term bed rest impairs amino acid-induced protein anabolism in humans.

Diminished muscular activity is associated with alterations of protein metabolism. The aim of this study was to evaluate the effect of short-term muscle inactivity on regulation of whole-body protein deposition during amino acid infusion to simulate an experimental postprandial state. We studied nine healthy young volunteers at the end of 14 day periods of strict bed rest and of controlled ambulation using a cross-over design. Subjects received a weight-maintaining diet containing 1 g protein kg(-1) day(-1). l[1-(13)C]leucine was used as a marker of whole-body protein kinetics in the postabsorptive state and during a 3 h infusion of an amino acid mixture (0.13 g amino acid (kg lean body mass)(-1) h(-1)). In the postabsorptive state, bed rest decreased (P < 0.05) the rate of leucine disposal (R(d)) to protein synthesis and tended to decrease leucine rate of appearance (R(a)) from proteolysis, whereas the rate of leucine oxidation did not change significantly. Amino acid infusion increased leucine R(d) to protein synthesis and oxidation and decreased leucine R(a) from proteolysis in both the bed rest and ambulatory conditions. Changes from basal in leucine R(d) to protein synthesis were lower (P < 0.05) during bed rest than those in the ambulatory period, whereas changes in leucine R(a) from proteolysis and oxidation were not significantly different. During amino acid infusion, net leucine deposition into body protein was 8 +/- 3% lower during bed rest than during the ambulatory phase. In conclusion, short-term bed rest leads to reduced stimulation of whole-body protein synthesis by amino acid administration. Results of this study were, in part, presented at the meeting, Experimental Biology, 2004, Washington DC.

Sensitivity of whole body protein synthesis to amino acid administration during short-term bed rest.

We tested the hypothesis that a reduced stimulation of whole-body protein synthesis by amino acid administration represents a major mechanism for the bed rest-induced loss of lean body mass. Healthy young subjects and matched controls were studied on the last day of a 14-day bed rest or ambulatory period, as part of the overall protocol "Short-term Bed Rest - Integrated Physiology" set up by the German Aerospace Centre (DLR) in co-operation with the European Space Agency. A balanced mixture of essential and non-essential amino acids was intravenously infused in the postabsorptive state for 3 hours at the rate of 0.1 g/kg/hour. The oxidative and non-oxidative (i.e., to protein synthesis) disposal of the infused leucine was determined by stable isotope and mass spectrometry techniques. The clearance of total infused amino acids tended to be greater (P=0.07) in the ambulatory group than in the bed rest group. When leucine clearance was partitioned between its oxidative and non-oxidative (i.e., to protein synthesis) components, the results indicated that the oxidative disposal was not statistically different in the bed rest and in the ambulatory groups. In contrast, the non-oxidative leucine disposal (i.e., to protein synthesis) was about 20% greater (P<0.01) in the ambulatory group than in the bed rest group. In conclusion, these preliminary data suggest that 14-day bed rest impairs the ability to utilise exogenous amino acids for protein synthesis.