Whole-body Protein Turnover Research Articles

Year‐long Changes in Protein Metabolism in Elderly Men and Women Supplemented With a Nutrition Cocktail of β‐Hydroxy‐β‐methylbutyrate (HMB), L‐Arginine, and L‐Lysine

A major contributing factor to the loss of mobility in elderly people is the gradual and continuous loss of lean body mass. To determine whether supplementation of an amino acid cocktail daily for 1 year could improve the age-associated changes in protein turnover and lean body mass in elderly people. Elderly (76+/-1.6 years) women (n=39) and men (n=38) were recruited for a double-blinded controlled study. Study participants were randomly assigned to either an isonitrogenous control-supplement (n=37) or a treatment-supplement (HMB/Arg/Lys) consisting of beta-hydroxy-beta-methylbutyrate, L-arginine, and L-lysine (n=40) for the 1-year study. Lean tissue mass was measured using both bioelectrical-impedance analysis (BIA) and dual energy x-ray absorptiometry (DXA). Rates of whole-body protein turnover were estimated using primed/intermittent oral doses of 15N-glycine. In subjects taking the HMB/Arg/Lys supplement, lean tissue increased over the year of study while in the control group, lean tissue did not change. Compared with control, HMB/Arg/Lys increased body cell mass (BIA) by 1.6% (P=.002) and lean mass (DXA) by 1.2% (P=.05). The rates of protein turnover were significantly increased 8% and 12% in the HMB/Arg/Lys-supplemented group while rates of protein turnover decreased 11% and 9% in the control-supplemented subjects (P<.01), at 3 and 12 months, respectively. Consumption of a simple amino acid-related cocktail increased protein turnover and lean tissue in elderly individuals in a year-long study.

Effects of dietary cysteamine supplementation on growth performance and whole-body protein turnover in finishing pigs

The objective of this study was to investigate the effects of dietary cysteamine (CS) supplementation on growth performance and whole-body protein turnover in finishing pigs. This experiment contained 2 trials with the first trial of effect of dietary cysteamine supplementation on growth performance in finishing pigs for 47 d. A total of 16 PIC pigs (60.02 ± 1.01 kg; eight gilts and eight barrows) were randomly assigned to one of two dietary groups, with four pens per group (per pen: one gilt, one barrow). In the second trial, a total of eight PIC barrows (60.04 ± 1.02 kg) were randomly assigned to one of the two dietary groups, with four pens/group (one pig/pen) for 37 d and then the eight barrows were housed individually in metabolism crates (four barrows in control group and four barrows in CS group) for 10 d. The pigs of the first and second trials were fed a basal diet containing 0 (control) or 70 mg CS/kg diet. A total of eight barrows of the second trial received a 7-d nitrogen balance trial. 15 N-Glycine (10 mg/kg BW) was gastrically infused after d 5 of the nitrogen balance trial. Feces and urine were collected daily to determine the N output. Results indicated that CS supplementation increased ( P < 0.05) average daily gain (ADG), feed intake (ADFI), nitrogen retention, nitrogen retention efficiency, and efficiency of digestible N utilization. In addition, CS supplementation resulted in a decreased ( P < 0.05) protein breakdown rate. Net protein gain in nitrogen was increased ( P < 0.05) by 63.5%. However, protein synthesis rate, nitrogen flux, and endogenous urinary nitrogen were not affected ( P > 0.05). It is concluded that dietary CS supplementation may improve growth performance in finishing pigs. Protein deposition is increased after dietary CS supplementation. This increase is caused by a decrease in protein breakdown.

Protein and Amino Acid Metabolism in the Human Newborn

Birth and adaptation to extrauterine life involve major shifts in the protein and energy metabolism of the human newborn. These include a shift from a state of continuous supply of nutrients including amino acids from the mother to cyclic periodic oral intake, a change in the redox state of organs, thermogenesis, and a significant change in the mobilization and use of oxidative substrates. The development of safe, stable isotopic tracer methods has allowed the study of protein and amino acid metabolism not only in the healthy newborn but also in those born prematurely and of low birth weight. These studies have identified the unique and quantitative aspects of amino acid/protein metabolism in the neonate, thus contributing to rational nutritional care of these babies. The present review summarizes the contemporary data on some of the significant developments in essential and dispensable amino acids and their relationship to overall protein metabolism. Specifically, the recent data of kinetics of leucine, phenylalanine, glutamine, sulfur amino acid, and threonine and their relation to whole-body protein turnover are presented. Finally, the physiological rationale and the impact of nutrient (amino acids) interventions on the dynamics of protein metabolism are discussed.

Increased Protein Turnover and Proteolysis Is an Early and Primary Feature of Short-Term Experimental Hyperthyroidism in Healthy Women

Hyperthyroidism increases energy expenditure, glucose turnover, lipolysis, and protein breakdown. Our objective was to test whether increased protein breakdown occurs independently of other catabolic effects in mild experimental hyperthyroidism. We conducted a single-blind, randomized, placebo-controlled, crossover study. Protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique ([(15)N]phenylalanine and [(2)H(4)]tyrosine). All subjects underwent a 3-h study in the basal state followed by a 3-h euglycemic clamp study. The study took place at a university clinical research unit. Eight healthy women (24-46 yr old) participated. Intervention included 6 d thyroid hormone (T(4) 50 microg and T(3) 0.67 microg/kg.d) or placebo administration. Thyroid hormone administration led to mild T(3) hyperthyroidism with more than a doubling of T(3) levels and suppression of TSH. Energy expenditure and body composition was unchanged. Glucose infusion rates, forearm glucose uptake, and levels of lipid intermediates were also alike. Basal whole-body phenylalanine flux and tyrosine flux (reflecting whole-body protein breakdown) were increased (P < 0.05) as were whole-body protein synthesis rate (P = 0.05). Basal forearm rate of appearance and disappearance for phenylalanine (reflecting muscle protein breakdown and synthesis) were similar. Mild short-term experimental hyperthyroidism increases whole-body protein turnover and breakdown before any measurable changes in energy expenditure or glucose and fat metabolism, suggesting that amino acid and protein metabolism is an early and primary target for thyroid hormone action in humans.

Whole-body protein turnover in peritoneal dialysis patients: a comparison of the [15N]glycine end product and the [13C]leucine precursor methods

Two well-described methods for measuring whole-body protein turnover (WBPT) are the precursor method using a primed continuous infusion of [1-(13)C]leucine and the end-product method with a single oral dose of [(15)N]glycine. We previously measured the effects of amino acid (AA)-containing dialysate on protein anabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using the [1-(13)C]leucine technique. Here, we examine whether the less invasive [(15)N]glycine method could also be appropriate for studying nutritional interventions. We compared the results of WBPT measurements using a single oral dose of [(15)N]glycine with those obtained with the primed continuous infusion of [1-(13)C]leucine during AA and glucose (G) dialysis and G-only dialysis in 12 CAPD patients in the fed state. The end-product method showed a wide variation for protein synthesis and breakdown measurements. It did not detect a small but significant increase in protein synthesis with AA-containing dialysate as shown by the precursor method. However, a significant relation was found between both methods for net protein synthesis (i.e. protein synthesis minus breakdown) during AA and G (r = 0.75, P = 0.005) or during G-only dialysis (r = 0.86, P < 0.001). The agreement between the two methods for the net protein balance was good [intra-class correlation coefficient (ICC) = 0.88] with G-only dialysate and moderate (ICC = 0.70) with AA and G dialysate. While the precursor method shows less variation, the more convenient end-product method may be useful in larger groups of selected patients including those on PD.

Increased Protein Maintains Nitrogen Balance during Exercise-Induced Energy Deficit

This study examined how a high-protein diet affected nitrogen balance and protein turnover during an exercise-induced energy deficit. Twenty-two men completed a 4-d (D1-4) baseline period (BL) of an energy balance diet while maintaining usual physical activity level, followed by 7 d (D5-11) of 1000 kcal.d increased energy expenditure via exercise (50-65% V O2peak). One group consumed 0.9 g of protein per kilogram per day and maintained energy balance throughout the 11-d intervention (BAL, N = 8). The other two groups consumed their BL energy intake throughout the 11 days, resulting in a 7-d, 1000-kcal.d energy deficit. These groups consumed either 0.9 g of protein per kilogram per day (DEF, N = 7) or 1.8 g of protein per kilogram per day (DEF-HP, N = 7). Mean nitrogen balance (NB), calculated per kilogram of fat-free mass (FFM), was determined for BL, days 5-8 (EX1), and days 9-11 (EX2). Whole-body protein turnover was derived from phenylalanine and tyrosine kinetics assessed while fasting at rest on days 4, 7, and 12, using a priming dose of L-[ring-N]tyrosine and a 4-h, primed, continuous infusion of L-[N]phenylalanine and L-[ring-H4]tyrosine. DEF experienced a decrease in NB from BL to EX 1 that was maintained in EX 2. No changes in NB occurred for BAL or DEF-HP over time. No within- or between-group differences were found over time for Phe flux (Qp), conversion rate of Phe to Tyr (Qpt), or the derived protein synthesis value (Sp). Increased dietary protein maintained NB during exercise-induced energy deficit, but this did not impact resting whole-body protein turnover.

Co-ingestion of leucine with protein does not further augment post-exercise muscle protein synthesis rates in elderly men

Leucine has been suggested to have the potential to modulate muscle protein metabolism by increasing muscle protein synthesis. The objective of this study was to investigate the surplus value of the co-ingestion of free leucine with protein hydrolysate and carbohydrate following physical activity in elderly men. Eight elderly men (mean age 73 +/- 1 years) were randomly assigned to two cross-over treatments consuming either carbohydrate and protein hydrolysate (CHO+PRO) or carbohydrate, protein hydrolysate with additional leucine (CHO+PRO+leu) after performing 30 min of standardized physical activity. Primed, continuous infusions with L-[ring-(13)C(6)]phenylalanine and L-[ring-(2)H(2)]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover as well as protein fractional synthetic rate in the vastus lateralis muscle over a 6 h period. Whole-body protein breakdown and synthesis rates were not different between treatments. Phenylalanine oxidation rates were significantly lower in the CHO+PRO+leu v. CHO+PRO treatment. As a result, whole-body protein balance was significantly greater in the CHO+PRO+leu compared to the CHO+PRO treatment (23.8 (SEM 0.3) v. 23.2 (SEM 0.3) micromol/kg per h, respectively; P < 0.05). Mixed muscle fractional synthetic rate averaged 0.081 (SEM 0.003) and 0.082 (SEM 0.006) %/h in the CHO+PRO+leu and CHO+PRO treatment, respectively (NS). Co-ingestion of leucine with carbohydrate and protein following physical activity does not further elevate muscle protein fractional synthetic rate in elderly men when ample protein is ingested.

Whole-body protein metabolism and energy expenditure in sheep selected for divergent wool production when fed above or below maintenance

Rates of whole-body protein turnover and energy expenditure were measured in two groups of wethers differing in estimated breeding values (EBVs) for wool growth, but with similar EBVs for fibre diameter and liveweight (LW). The sheep were offered a pelleted diet at 1.2 times their metabolisable energy (ME) requirement for maintenance (1.2 M) followed by either 0.8 M or 1.8 M for 5 weeks. In the 5th week, whole-body protein metabolism was estimated by using intravenous injection of 15N-glycine (g N/day) and whole-body energy expenditure rate (EE) was predicted by the CO2 entry rate technique using intravenous injection of NaH13CO3. The higher N intake (8.7 v. 20.4 g N/day, P &lt; 0.001) was associated with a higher whole-body protein flux (22.1 v. 34.2 g N/day, P &lt; 0.001), and a higher whole-body protein synthesis rate (17.0 v. 25.5 g N/day, P &lt; 0.001) and protein degradation rate (15.9 v. 20.7 g N/day, P &lt; 0.001). Irrespective of feeding levels, sheep with high-fleece EBVs (F+) synthesised and degraded more body protein N (g N/day) than sheep with low-fleece EBVs (F–), and F+ sheep also retained more ingested protein N (P &lt; 0.05) in wool and body tissue than F– sheep, but the significant differences due to genotypes disappeared when whole-body protein flux, synthesis and degradation were expressed as g N/kg LW0.75.day (metabolic weight). Estimates of EE were lower when the sheep were offered 0.8 M than when offered 1.8 M (5.85 v. 7.68 MJ/day, P &lt; 0.001) and were higher in F+ than in F– sheep (6.95 v. 6.58 MJ/day; P &lt; 0.05), but F+ sheep had a significantly lower (P &lt; 0.05) EE (MJ/kg LW0.75.day) than F– sheep. F+ animals also retained more energy in wool and wool-free body tissue than F– animals (P &lt; 0.05). The present study indicates that genetic selection for wool growth has resulted in increased efficiency of dietary protein and energy use for wool production and body-tissue growth in these sheep. Furthermore, there is no ‘trade off’ between deposition of nutrients in the body and wool in sheep with high EBVs for wool growth.

Effect of zinc supplementation on protein metabolism in late–middle-aged men: The Zenith study

Objective Zinc (Zn) is an essential trace element that is a potent enhancer of protein metabolism due to its numerous roles in metabolic processes. Protein turnover decreases with age. We determined whether a Zn supplementation, which increases serum Zn concentration and Zn exchangeable pool mass, modifies whole-body protein turnover and albumin and fibrinogen synthesis rates in late–middle-aged men. Methods Three groups of 16 healthy subjects 55–70 y of age participated in a randomized, doubled-blinded, placebo-controlled intervention. Each group received 0, 15, or 30 mg/d of supplemental Zn for 6 mo. At the end of the supplementation period, each subject received an intravenous infusion of L-[1- 13C] leucine to quantify whole-body leucine fluxes and synthesis rates of albumin and fibrinogen. Results In the placebo group, mean ± SEM whole-body leucine fluxes to protein synthesis, to oxidation, and from protein degradation were 1.46 ± 0.05, 0.40 ± 0.01, and 1.73 ± 0.06 μmol · kg −1 · min −1, respectively. Zn supplementation did not significantly change whole-body leucine fluxes. In the placebo group, plasma concentration and fractional rate of protein synthesis were 45 ± 1 g/L and 8.2 ± 0.6%/d for albumin and 3.6 ± 0.2 g/L and 16.7 ± 1.3%/d for fibrinogen, respectively. Zn supplementation did not significantly change these parameters or the absolute rates of synthesis of these proteins. Conclusion Increasing Zn supply does not modify whole-body protein metabolism and synthesis rates of albumin and fibrinogen in late–middle-aged men.

Determinants of Whole-Body Protein Metabolism in Subjects With and Without Type 2 Diabetes

Whole-body protein metabolism is abnormal in suboptimally controlled type 2 diabetes and obesity. We hypothesized that glycemia, insulin resistance, and waist circumference modulate these alterations in type 2 diabetes and, to a lesser extent, in individuals without type 2 diabetes. In 88 lean and obese subjects without and 40 with type 2 diabetes on an inpatient protein-controlled isoenergetic diet for 7 days, whole-body protein turnover was measured using the fed-fasted 60-h oral (15)N-glycine method. Nitrogen flux was determined from urinary (15)N urea and protein synthesis, breakdown and net balance calculated. Indexes of diabetes control, resting energy expenditure (REE), and body composition were assessed. Higher protein turnover in obese subjects was further increased, and net balance was lower in type 2 diabetes. Waist-to-hip ratio and ln homeostasis model assessment of insulin resistance (HOMA-IR) explained 40% of the variance in flux in type 2 diabetes; fat-free mass and lnHOMA-IR explained 62% in subjects without type 2 diabetes. Overall, fasting glucose explained 16% of the variance in net balance. In type 2 diabetes, net balance correlated negatively with fasting glucose in men and positively with hip circumference in women. Kinetics of whole-body protein metabolism are elevated, and net balance is diminished in type 2 diabetes, independently of obesity. Elevated flux is associated with greater visceral adiposity, REE, and insulin resistance of glucose. In type 2 diabetic men, these alterations worsened with magnitude of hyperglycemia. In type 2 diabetic women, larger hip circumferences may protect against such alterations. Our findings suggest that dietary protein requirements may be greater in type 2 diabetes to offset a reduced net balance, aggravated as glycemia increases, especially in men.

Influences of lipopolysaccharide-induced immune challenge on performance and whole-body protein turnover in weanling pigs

The objective of this study is to characterize the influence of immune stress induced by lipopolysaccharide (LPS) on protein utilization and turnover for early-weaned pigs. A total of 15, crossbred weanling pigs (initial body weight 10.15 ± 0.39 kg) were assigned to one of three treatments. Pigs were injected with LPS and fed ad libitum (LPS-challenge), or injected with endotoxin-free physiological salt solution (PSS) and fed ad libitum (control), or injected with PSS and fed the same amount of feed as LPS-challenged pigs (pair-feed). All pigs received a 4-d nitrogen balance trial. On d 1 and 3 of the trial, LPS-challenged pigs were injected intramuscularly with 200 μg/kg BW of LPS dissolved in 1 ml PSS. Pigs in other treatments were injected with 1 ml PSS. 15 N-Glycine (5 mg/kg BW) was gastrically infused after the second injection. Feces and urine were collected daily to determine the N output throughout the duration of the trial. Lymphocyte blastogenesis (LB) and serum immunoglobulins (IgA, IgG, IgM) were also detected to illustrate the LPS-induced immune responses. Results indicated that the injection of LPS significantly ( P < 0.01) elevated the LB and resulted in lower average daily gain (ADG), feed intake (ADFI) and efficiency of feed utilization than control pigs. Pair-fed pigs had higher performance than LPS-challenged pig but poorer than control pigs. Injection of LPS also resulted in significantly ( P < 0.01) lower nitrogen intake and efficiency of utilization than controls, and more fecal N excretion than Pair-fed pigs (3.19 ± 0.85 vs. 2.19 ± 0.67 g/d, P < 0.05). The whole-body nitrogen flux (4.34 ± 0.19 vs. 11.35 ± 0.12 g N/kg BW 0.75/d) and N accretion (5.57 ± 0.59 vs. 10.17 ± 1.12 g Pr/kg BW 0.75/d) were acutely ( P < 0.01) reduced as the feed intake decreased, but there was no significant difference between LPS-challenged and pair-fed pigs. Injection of LPS markedly ( P < 0.05) increased the protein degradation (16.76 ± 1.09 vs. 14.53 ± 1.24 g N/kg BW 0.75/d). It is concluded that LPS-induced immune challenge depresses growth performance and feed utilization efficiency by enhancing protein degradation rate and decreasing protein utilization for body protein retention.

Randomized clinical trial of the effect of preoperative oral carbohydrate treatment on postoperative whole-body protein and glucose kinetics

Preoperative oral carbohydrate (CHO) reduces postoperative insulin resistance. In this randomized trial, the effect of CHO on postoperative whole-body protein turnover was studied. Glucose and protein kinetics ([6,6(2)H(2)]D-glucose, [(2)H(5)]phenylalanine, [(2)H(2)]tyrosine and [(2)H(4)]tyrosine) and substrate oxidation (indirect calorimetry) were studied at baseline and during hyperinsulinaemic normoglycaemic clamping before and on the first day after colorectal resection. Fifteen patients were randomized to receive a preoperative beverage with high (125 mg/ml) or low (25 mg/ml) CHO content. Three patients were excluded after the intervention, leaving six patients in each group. After surgery whole-body protein balance did not change in the high oral CHO group, whereas it was more negative in the low oral CHO group after surgery at baseline (P = 0.003) and during insulin stimulation (P = 0.005). Insulin-stimulated endogenous glucose release was similar before and after surgery in the high oral CHO group, but was higher after surgery in the low oral CHO group (P = 0.013) and compared with the high oral CHO group (P = 0.044). Whole-body protein balance and the suppressive effect of insulin on endogenous glucose release are better maintained when patients receive a CHO-rich beverage before surgery.

Metabolic Effects of Oral Versus Transdermal Estrogen in Growth Hormone-Treated Girls with Turner Syndrome

Transdermal (TD) estrogen is often preferred over the oral route in postmenopausal and GH-deficient women taking estrogen, but this has not been studied in detail in girls. Our objective was to study the metabolic effects of oral vs. TD estrogen in GH-treated girls with Turner syndrome. Eleven girls with Turner syndrome, mean age 13.4 +/- 0.5 (se) yr, on GH for at least 6 months were recruited. Studies included [(13)C]leucine and d5-glycerol infusions, indirect calorimetry, dual-emission x-ray absorptiometry, and hormone and substrate measurements. They received, in random order, 17beta-estradiol orally (0.5, 1, and 2 mg for 2 wk each) and TD (0.025, 0.0375, and 0.05 mg for 2 wk each), and studies were repeated after each 6-wk course with 4 wk washout in between. Rates of whole-body protein turnover, oxidation and synthesis, lipolysis, lipid and carbohydrate oxidation, and resting energy expenditure were unaffected by either form of estrogen; nor were lipids, insulin, and fibrinogen concentrations affected. Plasma IGF-I concentrations did not change clinically significantly with either form of estrogen, despite higher estrogen concentrations after oral estrogen. Estradiol concentrations did not correlate with any variables measured. In GH-treated girls with Turner syndrome, neither oral nor TD estrogen adversely affected rates of protein turnover, lipolysis, and lipid oxidation rates or plasma lipids, fibrinogen, or fasting insulin concentrations. There was no clinically significant change in IGF-I concentrations after either form of estrogen. In aggregate, these data suggest that the route of delivery of estrogen does not adversely affect these metabolic effects of GH in young girls with Turner syndrome.

Growth Hormone Treatment in Adolescent Males with Idiopathic Short Stature: Changes in Body Composition, Protein, Fat, and Glucose Metabolism

Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH. Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion. Eight males with ISS (10.8-16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center. Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg.wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m(2).min) euglycemic clamp. GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels. Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance.

Co-ingestion Of Carbohydrate With Protein Does Not Stimulate Post-exercise Muscle Protein Synthesis Rates

Endurance athletes maximize post-exercise muscle glycogen synthesis by ingesting ample amounts of carbohydrate following exercise. In contrast, resistance athletes generally focus on protein intake during recovery to augment muscle protein anabolism. It has been suggested that both carbohydrate and protein should be ingested to maximize muscle protein synthesis rates. As many recreational athletes perform resistance type exercise for health and/or esthetic purposes, they generally prefer to restrict their caloric intake during recovery. Therefore, it is of importance to assess the need for co-ingestion of carbohydrate with protein on post-exercise muscle protein synthesis. PURPOSE: To determine the impact of the co-ingestion of different amounts of carbohydrate with protein on post-exercise muscle protein synthesis. METHODS: Ten healthy, untrained men were randomly assigned to 3 randomized cross-over trials. After 60 min of resistance exercise, subjects consumed 0.3 g·kg-1·h-1 protein hydrolysate with 0, 0.15 or 0.6 g·kg-1·h-1 carbohydrate during a 6 h recovery period (PRO, PRO+LCHO, and PRO+HCHO, respectively). Primed, continuous infusions of L-[ring-13C6]phenylalanine, L-[ring-2H2]tyrosine, and [6,6-2H2]glucose were applied, and blood and muscle samples were collected to assess whole-body protein turnover, glucose kinetics and fractional synthetic rate (FSR) in the vastus lateralis muscle over 6 h of recovery. RESULTS: Plasma insulin response was significantly higher in HCHO+PRO compared to LCHO+PRO and PRO (18.4±2.9 vs. 3.7±0.5 and 1.5±0.2 U·6h·L-1, respectively, P<0.001). Plasma glucose rate of appearance (Ra) and disappearance (Rd) increased over time in HCHO+PRO and LCHO+PRO but not in PRO. Plasma glucose Ra and Rd were substantially greater in HCHO+PRO vs. LCHO+PRO (P<0.01). Whole-body protein breakdown, synthesis and oxidation rates, as well as whole-body protein balance did not differ between trials. In accordance mixed muscle FSR did not differ between trials and averaged 0.114±0.010, 0.104±0.009% and 0.100±0.009%·h-1 in the HCHO+PRO, LCHO+PRO and PRO trial, respectively (NS). CONCLUSIONS: Co-ingestion of carbohydrate with an ample amount of protein hydrolysate (0.3 g·kg-1·h-1) does not further augment muscle protein synthesis rate during post-exercise recovery.

Aerobic Fitness Level Does Not Modulate Changes In Whole-body Protein Turnover Produced By Unaccustomed Increases In Energy Expenditure

Aerobic Fitness Level Does Not Modulate Changes In Whole-body Protein Turnover Produced By Unaccustomed Increases In Energy Expenditure

Lack of Effect of Acute Enteral Arginine Infusion on Whole-Body and Intestinal Protein Metabolism in Humans

Arginine is a conditionally essential amino acid and exerts anabolic effects. We studied the effects of enteral arginine on whole-body and duodenal protein metabolism. Eight healthy fasted volunteers received randomly a 5-hr enteral infusion of either arginine (Arg; 20 g) or an isonitrogenous amino acid mixture (AA) and an IV infusion of [13C]leucine. Duodenal biopsies were performed. Whole-body protein turnover and duodenal protein synthesis (FSR) were calculated from GC/MS-assessed enrichment. The mRNA levels for major components of proteolytic pathways, ubiquitin, cathepsin D, and m-calpain, were evaluated by RT-PCR. Results were compared using paired Wilcoxon test. Endogenous, oxidative, and nonoxidative leucine fluxes were not different after Arg and AA infusions, respectively. Duodenal mucosal protein FSR (71% +/- 26% vs 81% +/- 30%/day) and mRNA levels of ubiquitin, cathepsin D, and m-calpain were also similar after Arg and AA infusions. We conclude that in healthy subjects, arginine infusion exerts no effect on whole-body and duodenal protein metabolism. Whether arginine might specifically affect these parameters in catabolic or inflammatory situations remains to be determined.

Postexercise Whole-Body Protein Turnover Response to Three Levels of Protein Intake

This investigation examined the effect of variations in protein intake on whole-body protein turnover (WBPTO) after exercise in endurance-trained males. Five male runners (21.3 +/- 0.3 yr, 179 +/- 2 cm, 70.6 +/- 0.1 kg, 8.7 +/- 0.4% body fat, 70.6 +/- 0.1 VO2peak) participated in a randomized, crossover-design diet intervention, where they consumed either a low- (0.8 g.kg(-1); LP), moderate- (1.8 g.kg(-1); MP), or high-protein (3.6 g.kg(-1); HP) diet for 4 wk. WBPTO (Ra, leucine rate of appearance; NOLD, nonoxidative leucine disposal; and Ox, leucine oxidation) were assessed after a 75-min run at 70% VO2peak after each diet-intervention period. Leucine Ra (indicator of protein breakdown) and leucine Ox were greater on the HP diet than on the LP diet (Ra, 123.4 +/- 6.9 vs 97.9 +/- 6.0 micromol.kg(-1).h(-1); Ox, 23.9 +/- 0.5 vs 17.0 +/- 0.8 micromol.kg(-1).h(-1), P < 0.05). No differences were noted in NOLD (an indicator of protein synthesis) across diets. Plasma branched chain amino acids (BCAA) at rest were greater for MP and HP than for LP, and nonessential amino acids (NEAA) were greater for LP than MP at rest and greater than MP and HP after exercise. Findings from this study show that variations in protein intake can alter plasma amino acid levels and modulate rates of WBPTO after exercise. Additionally, a lower protein intake was associated with decreased rates of WBPTO after exercise.

Insulin resistance is associated with skeletal muscle protein breakdown in non-diabetic chronic hemodialysis patients

Deranged protein metabolism is known to complicate uremia. Insulin resistance is evident in chronic hemodialysis (CHD) patients. We hypothesized that the degree of insulin resistance would predict protein catabolism in non-diabetic CHD patients. We examined the relationship between Homeostasis Model Assessment (HOMA) and fasting whole-body and skeletal muscle protein turnover in 18 non-diabetic CHD patients using primed-constant infusions of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. Mean+/-s.d. fasting glucose and body mass index were 80.6+/-9.8 mg/dl and 25.4+/-4.4 kg/m(2), respectively. Median (interquartile range) HOMA was 1.6 (1.4, 3.9). Mean+/-s.e.m. skeletal muscle protein synthesis, breakdown, and net balance were 89.57+/-11.67, 97.02+/-13.3, and -7.44+/-7.14 microg/100 ml/min, respectively. Using linear regression, a positive correlation was observed between HOMA and skeletal muscle protein synthesis (R(2)=0.28; P=0.024), and breakdown (R(2)=0.49; P=0.001). An inverse association between net skeletal muscle protein balance and HOMA was also noted (R(2)=0.20; P=0.066). After adjustment for C-reactive protein, only the relationship between HOMA and skeletal muscle protein breakdown persisted (R(2)=0.49; P=0.006). There were no significant associations between components of whole-body protein turnover and HOMA. This study demonstrates that insulin resistance is evident in non-diabetic dialysis patients, is associated with skeletal muscle protein breakdown, and represents a novel target for intervention in uremic wasting.

Protein Metabolism and Endurance Exercise

Prolonged endurance exercise stimulates whole-body protein turnover (synthesis and degradation) but it remains contentious whether this translates into an increased net protein oxidation or dietary requirement for protein. Skeletal muscle is the major energy consumer during exercise and the oxidation of branched-chain amino acids (BCAA) is increased several-fold, suggesting an increased requirement for fuel. Increased BCAA oxidation has been proposed to impair aerobic energy provision during prolonged exercise, but there is little evidence to support this theory. Endurance training blunts the acute exercise-induced increase in whole-body protein turnover and skeletal BCAA oxidation at a given work intensity. However, training also increases the maximal capacity for skeletal muscle BCAA oxidation, as evidenced by a higher maximal activity of the rate-determining enzyme branched-chain oxo acid dehydrogenase. Exercise-induced changes in protein metabolism are affected by nutritional status, with high carbohydrate availability (as typically practiced by endurance athletes) generally associated with reduced net protein utilisation. Ingestion of protein with carbohydrate improves net protein balance during exercise and recovery compared with carbohydrate alone, but it remains to be determined whether this practice facilitates the adaptive response to chronic training.