The Fed-State Clamp Increases Whole-Body Protein Anabolism by Activation of Plasma and Muscle Protein Synthesis, in Healthy Men

2008 ◽  
Vol 32 (4) ◽  
pp. 341
Author(s):  
Stéphanie Chevalier ◽  
Olasunkanmi A.J. Adegoke ◽  
Linda Wykes ◽  
José A. Morais ◽  
Réjeanne Gougeon ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Body Protein ◽  
Fed State ◽  
Healthy Men

Protein coingestion stimulates muscle protein synthesis during resistance-type exercise

2008 ◽  
Vol 295 (1) ◽  
pp. E70-E77 ◽  
Author(s):  
Milou Beelen ◽  
René Koopman ◽  
Annemie P. Gijsen ◽  
Hanne Vandereyt ◽  
Arie K. Kies ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Protein Hydrolysate ◽  
Muscle Protein Synthesis ◽  
Nutritional Intervention ◽  
Whole Body ◽  
Exercise Session ◽  
Body Protein ◽  
Fed State ◽  
Breakdown Rates

In contrast to the effect of nutritional intervention on postexercise muscle protein synthesis, little is known about the potential to modulate protein synthesis during exercise. This study investigates the effect of protein coingestion with carbohydrate on muscle protein synthesis during resistance-type exercise. Ten healthy males were studied in the evening after they consumed a standardized diet throughout the day. Subjects participated in two experiments in which they ingested either carbohydrate or carbohydrate with protein during a 2-h resistance exercise session. Subjects received a bolus of test drink before and every 15 min during exercise, providing 0.15 g·kg−1·h−1 carbohydrate with (CHO + PRO) or without (CHO) 0.15 g·kg−1·h−1 protein hydrolysate. Continuous intravenous infusions with l-[ ring-13C6]phenylalanine and l-[ ring-2H2]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body and muscle protein synthesis rates during exercise. Protein coingestion lowered whole body protein breakdown rates by 8.4 ± 3.6% ( P = 0.066), compared with the ingestion of carbohydrate only, and augmented protein oxidation and synthesis rates by 77 ± 17 and 33 ± 3%, respectively ( P < 0.01). As a consequence, whole body net protein balance was negative in CHO, whereas a positive net balance was achieved after the CHO + PRO treatment (−4.4 ± 0.3 vs. 16.3 ± 0.4 μmol phenylalanine·kg−1·h−1, respectively; P < 0.01). In accordance, mixed muscle protein fractional synthetic rate was 49 ± 22% higher after protein coingestion (0.088 ± 0.012 and 0.060 ± 0.004%/h in CHO + PRO vs. CHO treatment, respectively; P < 0.05). We conclude that, even in a fed state, protein coingestion stimulates whole body and muscle protein synthesis rates during resistance-type exercise.

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis

1981 ◽  
Vol 241 (4) ◽  
pp. E321-E327 ◽  
Author(s):  
M. N. Goodman ◽  
M. A. McElaney ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Early Event ◽  
Body Protein ◽  
Fed State ◽  
Prolonged Starvation ◽  
Obese Rats ◽  
Old Rats

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

scholarly journals Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men

2009 ◽  
Vol 296 (1) ◽  
pp. E105-E113 ◽  
Author(s):  
Olasunkanmi A. J. Adegoke ◽  
Stéphanie Chevalier ◽  
José A. Morais ◽  
Réjeanne Gougeon ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Cellular Mechanisms ◽  
Body Protein ◽  
Fed State ◽  
Mtorc1 Signaling

Since maximum anabolism occurs postprandially, we developed a simulated fed state with clamped hyperinsulinemia, physiological hyperglycemia, and hyperaminoacidemia (Hyper-3) and explored muscle cellular mechanisms. Whole body [1-13C]leucine and [3-3H]glucose kinetics in healthy men were compared between hyperinsulinemic, euglycemic, isoaminoacidemic (Hyper-1, n = 10) and Hyper-3 ( n = 9) clamps. In Hyper-3 vs. Hyper-1, nonoxidative leucine Rd [rate of disappearance (synthesis)] was stimulated more (45 ± 4 vs. 24 ± 4 μmol/min, P < 0.01) and endogenous Ra [rate of appearance (breakdown)] was inhibited similarly; hence net balance increased more (86 ± 6 vs. 49 ± 2 μmol/min, P < 0.001). Glucose Rd was similar; thus Hyper-3 metabolic clearance rate (331 ± 23 vs. 557 ± 41 ml/min, P < 0.0005) and Rd/insulin (M, 0.65 ± 0.10 vs. 1.25 ± 0.10 mg·min−1·pmol−1·l, P < 0.001) were less, despite higher insulin (798 ± 74 vs. 450 ± 24 pmol/l, P < 0.005). In vastus lateralis muscle biopsies, phosphorylation of Akt ( P = 0.025), mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K1; P = 0.008), S6 ( P = 0.049), and 4E-binding protein 1 (4E-BP1; P = 0.001) increased. With decreased eukaryotic initiation factor-4E (eIF4E)·4E-BP1 complex ( P = 0.01), these are consistent with increased mTOR complex 1 (mTORC1) signaling and translation initiation of protein synthesis. Although mRNA expression of ubiquitin, MAFbx 1, and MuRF-1 was unchanged, total ubiquitinated proteins decreased 20% ( P < 0.01), consistent with proteolysis suppression. The Hyper-3 clamp increases whole body protein synthesis, net anabolism, and muscle protein translation initiation pathways and decreases protein ubiquitination. The main contribution of hyperaminoacidemia is stimulation of synthesis rather than inhibition of proteolysis, and it attenuates the expected increment of glucose disposal.

scholarly journals Dose-response effects of dietary protein on muscle protein synthesis during recovery from endurance exercise in young men: a double-blind randomized trial

2020 ◽  
Vol 112 (2) ◽  
pp. 303-317 ◽  
Author(s):  
Tyler A Churchward-Venne ◽  
Philippe J M Pinckaers ◽  
Joey S J Smeets ◽  
Milan W Betz ◽  
Joan M Senden ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
G Protein ◽  
Endurance Exercise ◽  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mitochondrial Protein ◽  
Whole Body ◽  
Double Blind ◽  
Body Protein

ABSTRACT Background Protein ingestion increases skeletal muscle protein synthesis rates during recovery from endurance exercise. Objectives We aimed to determine the effect of graded doses of dietary protein co-ingested with carbohydrate on whole-body protein metabolism, and skeletal muscle myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis rates during recovery from endurance exercise. Methods In a randomized, double-blind, parallel-group design, 48 healthy, young, endurance-trained men (mean ± SEM age: 27 ± 1 y) received a primed continuous infusion of l-[ring-2H5]-phenylalanine, l-[ring-3,5-2H2]-tyrosine, and l-[1-13C]-leucine and ingested 45 g carbohydrate with either 0 (0 g PRO), 15 (15 g PRO), 30 (30 g PRO), or 45 (45 g PRO) g intrinsically l-[1-13C]-phenylalanine and l-[1-13C]-leucine labeled milk protein after endurance exercise. Blood and muscle biopsy samples were collected over 360 min of postexercise recovery to assess whole-body protein metabolism and both MyoPS and MitoPS rates. Results Protein intake resulted in ∼70%–74% of the ingested protein-derived phenylalanine appearing in the circulation. Whole-body net protein balance increased dose-dependently after ingestion of 0, 15, 30, or 45 g protein (mean ± SEM: −0.31± 0.16, 5.08 ± 0.21, 10.04 ± 0.30, and 13.49 ± 0.55 μmol phenylalanine · kg−1 · h−1, respectively; P &lt; 0.001). 30 g PRO stimulated a ∼46% increase in MyoPS rates (%/h) compared with 0 g PRO and was sufficient to maximize MyoPS rates after endurance exercise. MitoPS rates were not increased after protein ingestion; however, incorporation of dietary protein–derived l-[1-13C]-phenylalanine into de novo mitochondrial protein increased dose-dependently after ingestion of 15, 30, and 45 g protein at 360 min postexercise (0.018 ± 0.002, 0.034 ± 0.002, and 0.046 ± 0.003 mole percentage excess, respectively; P &lt; 0.001). Conclusions Protein ingested after endurance exercise is efficiently digested and absorbed into the circulation. Whole-body net protein balance and dietary protein–derived amino acid incorporation into mitochondrial protein respond to increasing protein intake in a dose-dependent manner. Ingestion of 30 g protein is sufficient to maximize MyoPS rates during recovery from a single bout of endurance exercise. This trial was registered at trialregister.nl as NTR5111.

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

2005 ◽  
Vol 288 (4) ◽  
pp. E645-E653 ◽  
Author(s):  
René Koopman ◽  
Anton J. M. Wagenmakers ◽  
Ralph J. F. Manders ◽  
Antoine H. G. Zorenc ◽  
Joan M. G. Senden ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Vastus Lateralis Muscle ◽  
Protein Balance ◽  
Body Protein ◽  
Breakdown Rates ◽  
Postexercise Recovery ◽  
Male Subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of l-[ ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 ± 19% and +77 ± 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial ( P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials ( P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 ± 0.006 vs. 0.061 ± 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 ± 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.

scholarly journals Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2457 ◽  
Author(s):  
Jess A. Gwin ◽  
David D. Church ◽  
Robert R. Wolfe ◽  
Arny A. Ferrando ◽  
Stefan M. Pasiakos
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Energy Deficit ◽  
Whole Body ◽  
Intact Protein ◽  
Body Protein ◽  
Protein Feeding

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20–25 g whey protein, 0.25–0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit.

scholarly journals Increased plasma Gln and Leu Raand inappropriately low muscle protein synthesis rate in AIDS wasting

1998 ◽  
Vol 275 (4) ◽  
pp. E577-E583 ◽  
Author(s):  
Kevin E. Yarasheski ◽  
Jeffrey J. Zachwieja ◽  
Jennifer Gischler ◽  
Jan Crowley ◽  
Mary M. Horgan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Asymptomatic Group ◽  
Body Protein ◽  
Asymptomatic Subjects ◽  
Muscle Protein Synthesis Rate

Muscle protein wasting occurs in human immunodeficiency virus (HIV)-infected individuals and is often the initial indication of acquired immunodeficiency syndrome (AIDS). Little is known about the alterations in muscle protein metabolism that occur with HIV infection. Nine subjects with AIDS wasting (CD4 < 200/mm3), chronic stable opportunistic infections (OI), and ≥10% weight loss, fourteen HIV-infected men and one woman (CD4 > 200/mm3) without wasting or OI (asymptomatic), and six HIV-seronegative lean men (control) received a constant intravenous infusion of [1-13C]leucine (Leu) and [2-15N]glutamine (Gln). Plasma Leu and Gln rate of appearance (Ra), whole body Leu turnover, disposal and oxidation rates, and [13C]Leu incorporation rate into mixed muscle protein were assessed. Total body muscle mass/fat-free mass was greater in controls (53%) than in AIDS wasting (43%; P = 0.04). Fasting whole body proteolysis and synthesis rates were increased above control in the HIV+ asymptomatic group and in the AIDS-wasting group ( P = 0.009). Whole body Leu oxidation rate was greater in the HIV+ asymptomatic group than in the control and AIDS-wasting groups ( P < 0.05). Fasting mixed muscle protein synthesis rate was increased in the asymptomatic subjects (0.048%/h; P = 0.01) but was similar in AIDS-wasting and control subjects (0.035 vs. 0.037%/h). Plasma Gln Rawas increased in AIDS-wasting subjects but was similar in control and HIV+ asymptomatic subjects ( P < 0.001). These findings suggest that AIDS wasting results from 1) a preferential reduction in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle protein synthesis while whole body protein synthesis is increased, and 3) a significant increase in Gln release into the circulation, probably from muscle. Several interesting explanations for the increased Gln Rain AIDS wasting exist.

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

1996 ◽  
Vol 270 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
A. A. Ferrando ◽  
H. W. Lane ◽  
C. A. Stuart ◽  
J. Davis-Street ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Whole Body ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Model Calculations ◽  
Body Protein

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Muscle wasting in emphysema

1988 ◽  
Vol 75 (4) ◽  
pp. 415-420 ◽  
Author(s):  
W. L. Morrison ◽  
J. N. A. Gibson ◽  
C. Scrimgeour ◽  
M. J. Rennie
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Myofibrillar Protein ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise

1996 ◽  
Vol 81 (5) ◽  
pp. 2034-2038 ◽  
Author(s):  
Kevin D. Tipton ◽  
Arny A. Ferrando ◽  
Bradley D. Williams ◽  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Resistance Training ◽  
Endurance Exercise ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Muscle Protein Metabolism

Tipton, Kevin D., Arny A. Ferrando, Bradley D. Williams, and Robert R. Wolfe. Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise. J. Appl. Physiol. 81(5): 2034–2038, 1996.—There is little known about the responses of muscle protein metabolism in women to exercise. Furthermore, the effect of adding resistance training to an endurance training regimen on net protein anabolism has not been established in either men or women. The purpose of this study was to quantify the acute effects of combined swimming and resistance training on protein metabolism in female swimmers by the direct measurement of muscle protein synthesis and whole body protein degradation. Seven collegiate female swimmers were each studied on four separate occasions with a primed constant infusion of ring-[13C6]phenylalanine (Phe) to measure the fractional synthetic rate (FSR) of the posterior deltoid and whole body protein breakdown. Measurements were made over a 5-h period at rest and after each of three randomly ordered workouts: 1) 4,600 m of intense interval swimming (SW); 2) a whole body resistance-training workout with no swimming on that day (RW); and 3) swimming and resistance training combined (SR). Whole body protein breakdown was similar for all treatments (0.75 ± 0.04, 0.69 ± 0.03, 0.69 ± 0.02, and 0.71 ± 0.04 μmol ⋅ min−1 ⋅ kg−1for rest, RW, SW, and SR, respectively). The FSR of the posterior deltoid was significantly greater ( P< 0.05) after SR (0.082 ± 0.015%/h) than at rest (0.045 ± 0.006%/h). There was no significant difference in the FSR after RW (0.048 ± 0.004%/h) or SW (0.064 ± 0.008%/h) from rest or from SR. These data indicate that the combination of swimming and resistance exercise stimulates net muscle protein synthesis above resting levels in female swimmers.

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