Increase In Whole-body Protein Synthesis Research Articles

Application of a stoichiometric bioenergetic approach and whole-body protein synthesis to the nutritional assessment of juvenile Thenus australiensis

The present study successfully combined a stoichiometric bioenergetic approach with an endpoint stochastic model to simultaneously determine specific dynamic action, metabolic substrate use and whole-body protein synthesis in juvenile slipper lobster Thenus australiensis. Juvenile lobsters were fasted for 48 h to investigate routine metabolism before receiving a single meal of formulated feed containing 1% 15N-labeled Spirulina. Postprandial oxygen consumption rate, dissolved inorganic carbon, and total nitrogen excretion returned to the pre-feeding level within 24 h. The rate of whole-body protein synthesis was 0.76 ± 0.15 mg CP g−1 day−1, with a significant reduction from 24 to 48 h post-feeding. The postprandial increase in whole-body protein synthesis accounted for 13–19% of total oxygen uptake. Protein was the primary energy substrate for 48 h fasted (45% oxygen consumption) and post-feeding lobster (44%), suggesting that dietary protein was not efficiently used for growth. The secondary energy substrate differed between carbohydrates in 48 h fasted and lipids in post-feeding lobsters. The present study recommends integrating protein synthesis into protein requirement experiments of marine ectotherms to acquire a more comprehensive picture of protein and energy metabolism and nutritional physiology crucial for formulating cost-effective aquafeeds.

Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease.

Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB), and SM protein turnover in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic-euglycemic-euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients. During dual clamp, controls had a higher increase in WB protein synthesis and a higher suppression of WB protein breakdown compared with MHD patients, resulting in statistically significantly more positive WB protein net balance [2.02 (interquartile range [IQR]: 1.79 and 2.36) vs. 1.68 (IQR: 1.46 and 1.91) mg·kg fat-free mass-1·min-1 for controls vs. for MHD patients, respectively, P < 0.001]. At baseline, SM protein synthesis and breakdown rates were higher in MHD patients versus controls, but SM net protein balance was similar between groups. During dual clamp, SM protein synthesis increased statistically significantly more in controls compared with MHD patients ( P = 0.03), whereas SM protein breakdown decreased comparably between groups. SM net protein balance was statistically significantly more positive in controls compared with MHD patients [67.3 (IQR: 46.4 and 97.1) vs. 15.4 (IQR: -83.7 and 64.7) μg·100 ml-1·min-1 for controls and MHD patients, respectively, P = 0.03]. Human SM biopsy showed a positive correlation between glucose and leucine disposal rates, phosphorylated AKT to AKT ratio, and muscle mitochondrial markers in controls but not in MHD patients. Diminished response to anabolic actions of insulin in the stimulated setting could lead to muscle wasting in MHD patients.

Protein Requirements of the Critically Ill Pediatric Patient.

This article includes a review of protein needs in children during health and illness, as well as a detailed discussion of protein metabolism, including nitrogen balance during critical illness, and assessment and prescription/delivery of protein to critically ill children. The determination of protein requirements in children has been difficult and challenging. The protein needs in healthy children should be based on the amount needed to ensure adequate growth during infancy and childhood. Compared with adults, children require a continuous supply of nutrients to maintain growth. The protein requirement is expressed in average requirements and dietary reference intake, which represents values that cover the needs of 97.5% of the population. Critically ill children have an increased protein turnover due to an increase in whole-body protein synthesis and breakdown with protein degradation leading to loss of lean body mass (LBM) and development of growth failure, malnutrition, and worse clinical outcomes. The results of protein balance studies in critically ill children indicate higher protein needs, with infants and younger children requiring higher intakes per body weight compared with older children. Monitoring the side effects of increased protein intake should be performed. Recent studies found a survival benefit in critically ill children who received a higher percentage of prescribed energy and protein goal by the enteral route. Future randomized studies should evaluate the effect of protein dosing in different age groups on patient outcomes, including LBM, muscle structure and function, duration of mechanical ventilation, intensive care unit and hospital length of stay, and mortality.

Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease

Background:It is often suggested that chronic wasting diseases [eg, chronic obstructive pulmonary disease (COPD)] may benefit from branched-chain amino acid (BCAA) administration via improved protein metabolism.Objective:The aim was to examine whether adding BCAAs to a soy protein meal would enhance protein anabolism in COPD patients and in healthy elderly persons.Design:Eight normal-weight COPD patients and 8 healthy control subjects were examined on 2 test days. Simultaneous continuous intravenous infusion of l-[ring-2H5]phenylalanine (Phe) and l-[ring-2H2]tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy + BCAA protein meal (rate of ingestion: 0.02 g protein·kg body weight−1·20 min−1) in a crossover design. Together with the meal, oral ingestion of 1-[13C]Phe was performed to measure first-pass Phe splanchnic extraction (SPEPhe). The endogenous rate of Phe appearance [reflecting whole-body protein breakdown (WbPB)], whole-body protein synthesis (WbPS), and net WbPS (WbPS − WbPB) were calculated. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses.Results:Soy feeding induced a reduction in WbPB and an increase in WbPS. BCAA supplementation of soy protein resulted in a significantly higher (P< 0.05) increase in WbPS than did soy protein alone in COPD patients but not in the healthy elderly. BCAA supplementation did not significantly alter the change in WbPB or net WbPS. Furthermore, BCAA supplementation decreased (absolute) SPEPhe(P< 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-related reduction in splanchnic protein synthesis.Conclusion:BCAA supplementation to soy protein enhances WbPS in patients with COPD and alters interorgan protein metabolism in favor of the peripheral (muscle) compartment in healthy elderly and even more in COPD patients.

Altered interorgan response to feeding in patients with chronic obstructive pulmonary disease

Previously, we reported increased values for whole-body protein turnover in patients with chronic obstructive pulmonary disease (COPD) in the postabsorptive state. The objective was to investigate whether intake of a carbohydrate-protein meal influences whole-body protein turnover differently in COPD patients and control subjects. Eight normal-weight patients with moderate COPD and 8 healthy control subjects were examined in the postabsorptive state and after 2 h of repeatedly ingesting a maltodextrin casein-based protein meal (0.02 g x kg body wt(-1) x 20 min(-1)). Combined simultaneous, continuous, intravenous infusion of L-[ring-2H5]-phenylalanine and L-[ring-2H2]-tyrosine tracer and oral repeated ingestion of 1-13C-phenylalanine were performed to measure whole-body protein synthesis (WbPS) and first-pass splanchnic extraction of phenylalanine. Endogenous rate of appearance of phenylalanine as the measure of whole-body protein breakdown (WbPB) and netWbPS was calculated as WbPS--WbPB. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. Feeding induced an increase in WbPS and a reduction in WbPB. The reduction in WbPB was larger in the COPD group than in the control group (P < 0.05) and was related to the lower splanchnic extraction of phenylalanine in the patients. Consequently, netWbPS increased more after feeding in the COPD group than in the control group (P < 0.05). Feeding induces more protein anabolism in normal-weight patients with moderate COPD than in healthy control subjects. This is probably because these COPD patients are characterized by an adaptive interorgan response to feeding to prevent or delay weight loss at this disease stage.

Altered interorgan response to feeding in patients with chronic obstructive pulmonary disease

Background: Previously, we reported increased values for whole-body protein turnover in patients with chronic obstructive pulmonary disease (COPD) in the postabsorptive state. Objective: The objective was to investigate whether intake of a carbohydrate-protein meal influences whole-body protein turnover differently in COPD patients and control subjects. Design: Eight normal-weight patients with moderate COPD and 8 healthy control subjects were examined in the postabsorptive state and after 2 h of repeatedly ingesting a maltodextrin casein-based protein meal (0.02 g · kg body wt−1 · 20 min−1). Combined simultaneous, continuous, intravenous infusion of l-[ring-2H5]-phenylalanine and l-[ring-2H2]-tyrosine tracer and oral repeated ingestion of 1-13C-phenylalanine were performed to measure whole-body protein synthesis (WbPS) and first-pass splanchnic extraction of phenylalanine. Endogenous rate of appearance of phenylalanine as the measure of whole-body protein breakdown (WbPB) and netWbPS was calculated as WbPS − WbPB. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. Results: Feeding induced an increase in WbPS and a reduction in WbPB. The reduction in WbPB was larger in the COPD group than in the control group (P < 0.05) and was related to the lower splanchnic extraction of phenylalanine in the patients. Consequently, netWbPS increased more after feeding in the COPD group than in the control group (P < 0.05). Conclusion: Feeding induces more protein anabolism in normal-weight patients with moderate COPD than in healthy control subjects. This is probably because these COPD patients are characterized by an adaptive interorgan response to feeding to prevent or delay weight loss at this disease stage.

Growth hormone modulates amino acid oxidation in the surgical patient: Leucine kinetics during the fasted and fed state using moderate nitrogenous and caloric diet and recombinant human growth hormone

Twelve patients (aged 70 ± 9 years) who were scheduled for resection of rectosigmoid colon adenocarcinoma but were otherwise healthy were randomly allocated after surgery to receive either peripheral parenteral nutrition alone ([PPN] n = 6) or in combination with recombinant human growth hormone (rGH) at a daily dose of 0.15 U · kg −1 · d −1 (PPN + rGH, n = 6). The daily nutritional regimen was 0.1 g nitrogen · kg −1 · d −1 and 20 kcal · kg −1 · d −1 (nonprotein energy was supplied as 60% lipid and 40% carbohydrate), and it was maintained for 6 days before and 6 days after surgery. Protein kinetics were studied in all 12 patients during the fasted and fed states before and 6 days after surgery using an 8-hour 13C-leucine tracer infusion. Daily urinary nitrogen, gaseous exchange, and plasma insulin, growth hormone, and insulin-like growth factor-I (IGF-I) were determined before and after surgery. Surgery was responsible for significant increases in postabsorptive whole-body protein flux and synthesis and leucine oxidation ( P < .01). Supplementation of PPN with rGH contributed to a significant attenuation of the postoperative increase in leucine oxidation ( P = .02), with a significant increase in whole-body protein synthesis ( P = .02) and no effect on protein breakdown ( P = .40). During the fed state, leucine oxidation increased significantly ( P =.005), with the greatest change occurring in the PPN group. Feeding was associated with a significant decrease in whole-body protein breakdown before and after surgery in both groups ( P = .001). Postoperative urinary nitrogen excretion was lower but was not statistically significant in the PPN + rGH group compared with the PPN group. There was a significant increase in oxygen consumption (Vo 2) and carbon dioxide production (Vco 2) as a result of feeding and surgery ( P < .01). Supplementation with rGH caused a decrease in the respiratory quotient (RQ) ( P = .04), particularly after surgery, indicating a direct effect of rGH on fatty acid oxidation. Circulating plasma insulin increased significantly in both groups with feeding and rGH supplementation ( P < .05). This was enhanced after surgery, particularly in the rGH group ( P < .05). Plasma growth hormone decreased after surgery in the PPN group ( P < .05), but did not change as a result of feeding. The circulating levels increased in the PPN + rGH group following subcutaneous administration before or after surgery. Plasma IGF-I decreased after surgery in the PPN group ( P < .05), and no changes occurred in the PPN + rGH group with feeding. The present findings suggest a distinct positive effect of rGH on protein synthesis in catabolic patients receiving a moderate intake of nitrogen and calories. This is achieved by modulation of amino acid oxidation. The acute effect of intravenous (IV) nutrients on protein metabolism during the catabolic phase of surgical stress caused a direct decrease in protein breakdown with no effect on protein synthesis.

Protein metabolism and liver disease

In health, the liver orchestrates the metabolism of proteins and amino acids. When the liver is diseased, the regulation of protein metabolism is frequently disturbed. The manifestations of disturbed protein metabolism in liver disease are varied and change with disease aetiology and severity. The hallmarks of protein and amino acid metabolism in liver disease are lowered concentrations of circulating branched-chain and increased concentrations of circulating aromatic amino acids with concomitantly altered amino acid kinetics. The changes in amino acid kinetics in liver disease are characterized by increased endogenous leucine flux, an indicator of protein breakdown, and leucine oxidation in the post-absorptive state (when calculated using a reciprocal-pool model and normalized for body cell mass). In addition, the increase in whole-body protein synthesis in response to an amino acid infusion may be attenuated in patients with cirrhosis. These changes are often accompanied by clinically apparent muscle wasting, manifest as protein-calorie malnutrition, and associated low levels of hepatically synthesized plasma proteins. While the pathogenesis of these changes in protein and amino acid metabolism has not been elucidated, altered levels of circulating hormones, known to affect protein metabolism, are probably important. Lowered levels of micronutrients and trace metals and elevated levels of cytokines may also play a role.

Effect of increased protein intake and nutritional status on whole-body protein metabolism of aids patients with weight loss

The aim of this study was to investigate nutritional status and protein metabolism during total parenteral nutrition (TPN) in AIDS patients with weight loss. Six patients on treatment for AIDS-associated complications were investigated and received TPN that supplied energy equivalent to 1.5 times the resting energy expenditure (REE). Amino acid (AA) supply increased from 0.6 g/kg body weight (BW)/d on days 1 to 3 and 1.2 on days 4 to 6 to 1.8 on days 7 to 9. Nonprotein energy was given as equicaloric amounts of glucose and fat emulsion. There were repeated measurements of nitrogen balance and whole-body protein turnover (WBPT) using a bolus 15 N-glycine method on the morning of days 3, 6, and 9. Principal findings were as follows: (1) increasing the supply of AAs significantly improves nitrogen balance in AIDS patients; (2) there is no simple linear effect of increasing amounts of AAs on WBPT in AIDS patients; (3) WBPT is high and variable in these patients; and (4) mean WBPT of each patient is significantly correlated with body cell mass (BCM) as a proportion of BW ( P < .001, r = .92). We conclude that poor nutritional status in AIDS patients with weight loss is associated with high WBPT. However, these patients can attain at least transiently positive nitrogen balance with sufficient protein intake, predominantly through an increase in whole-body protein synthesis (WBPS).

Sparrows increase their rates of tissue and whole-body protein synthesis during the annual molt

Avian molt is a period of adult growth involving mainly the deposition of keratins. The energy contained in newly synthesized plumage is small compared with the energy expended for molt, resulting in a low energetic efficiency for keratin deposition (as low as 3%). We measured the fractional synthesis rates (FSR) of tissue and whole-body protein in molting and non-molting sparrows using the “flooding dose” method to determine if part of the energetic cost of avian molt might be accounted for by an accelerated rate of whole-body protein turnover. Molting sparrows had significantly higher FSR of protein in liver, muscle, and whole-body (excluding the integument) throughtout the 24 hr cycle compared with values for non-molting sparrows. In absolute terms, molting sparrows synthesized daily 260 mg of body protein (excluding keratins) above that synthesized by non-molting sparrows. The daily increase in whole-body protein synthesis in molting birds equaled at least 3.5-fold the amount of protein synthesized and deposited as keratin per day (75 mg) during the most intensive phase of molt. This accelerated rate of whole-body protein synthesis undoubtedly contributes significantly to the energetic costs of molt.

Whole-body protein kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion and total parenteral nutrition.

We have isotopically determined rates of whole-body protein synthesis and catabolism in a group of normal volunteers and in two groups of cancer patients: 20 patients with advanced weight-loss (AWL) upper gastrointestinal cancer and 7 patients with early non-weight-loss (ENWL) lower gastrointestinal cancer. In both patients and volunteers we determined protein kinetics in the basal state and during glucose infusion at 4 mg/kg/min. In addition, in the AWL patients the effect of total parenteral nutrition (TPN) on protein dynamics was also assessed. The rate of net protein breakdown was determined with the primed constant infusion of either 15N-urea or 14C-urea, the rate of whole-body protein catabolism was measured with the primed constant infusion of 15N-lysine, and the rate of whole-body protein synthesis was deduced from the above two values. The basal rates of net protein catabolism, whole-body protein catabolism, and whole-body protein synthesis were similar in the volunteers and ENWL cancer patients. The basal values for net protein catabolism in the volunteers and ENWL patients were 1.46 +/- 0.18 and 1.34 +/- 0.08 gm/kg/min, respectively. In both volunteers and ENWL patients glucose infusion resulted in a significant decrease in net protein catabolism. In the ENWL patients this decrease was due to a significant decrease in whole-body protein catabolism (p less than 0.05); the rate of whole-body protein synthesis did not change significantly. In the AWL cancer patients the rate of net protein catabolism was significantly higher than in either the volunteer or ENWL group (p less than 0.05), and glucose infusion did not result in a decrease in net protein catabolism. However, when the AWL group was studied during TPN there was a significant decrease in net protein catabolism from 2.24 +/- 0.30 to 0.17 +/- 0.09 gm/kg/day (p less than 0.01). This decrease was due to the combined effect of a significant decrease in whole-body protein catabolism coupled with an increase in whole-body protein synthesis. From these studies we conclude the following: (1) ENWL cancer patients and normal volunteers have similar protein dynamics, and in both groups glucose infusion resulted in a significant decrease in protein loss. (2) AWL cancer patients have an elevated rate of net protein catabolism, and this is not sensitive to glucose infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

GLUCOSE PROMOTES WHOLE-BODY PROTEIN SYNTHESIS FROM INFUSED AMINOACIDS IN FASTING MAN: Isotopic Demonstration

15N-glycine constant infusion, with plateau urea enrichment as the endpoint, demonstrated a clear increase in whole-body protein synthesis when glucose was added to aminoacid infusion in fasting men. Whole-body protein-breakdown rates remained unchanged. There was an unexpected fall in whole-body nitrogen turnover when the subjects were changed from an oral intake to either of the intravenous programmes: this finding, not previously reported, may be due to the decrease in gastrointestinal enzyme synthesis and intestinal-lining cell-turnover when oral intake is replaced by total parenteral nutrition.