Mixed Muscle Protein Synthesis Rates Research Articles

A well-balanced vegan diet does not compromise daily mixed muscle protein synthesis rates when compared to an omnivorous diet in active older adults: a randomized controlled cross-over trial

A well-balanced vegan diet does not compromise daily mixed muscle protein synthesis rates when compared to an omnivorous diet in active older adults: a randomized controlled cross-over trial

Potato Protein Ingestion Increases Muscle Protein Synthesis Rates at Rest and during Recovery from Exercise in Humans.

ABSTRACTIntroductionPlant-derived proteins have received considerable attention as an alternative to animal-based proteins and are now frequently used in both plant-based diets and sports nutrition products. However, little information is available on the anabolic properties of potato-derived protein. This study compares muscle protein synthesis rates after the ingestion of 30 g potato protein versus 30 g milk protein at rest and during recovery from a single bout of resistance exercise in healthy, young males.MethodsIn a randomized, double-blind, parallel-group design, 24 healthy young males (24 ± 4 yr) received primed continuous l-[ring-13C6]-phenylalanine infusions while ingesting 30 g potato-derived protein or 30 g milk protein after a single bout of unilateral resistance exercise. Blood and muscle biopsies were collected for 5 h after protein ingestion to assess postprandial plasma amino acid profiles and mixed muscle protein synthesis rates at rest and during recovery from exercise.ResultsIngestion of both potato and milk protein increased mixed muscle protein synthesis rates when compared with basal postabsorptive values (from 0.020% ± 0.011% to 0.053% ± 0.017%·h−1 and from 0.021% ± 0.014% to 0.050% ± 0.012%·h−1, respectively; P < 0.001), with no differences between treatments (P = 0.54). In the exercised leg, mixed muscle protein synthesis rates increased to 0.069% ± 0.019% and 0.064% ± 0.015%·h−1 after ingesting potato and milk protein, respectively (P < 0.001), with no differences between treatments (P = 0.52). The muscle protein synthetic response was greater in the exercised compared with the resting leg (P < 0.05).ConclusionsIngestion of 30 g potato protein concentrate increases muscle protein synthesis rates at rest and during recovery from exercise in healthy, young males. Muscle protein synthesis rates after the ingestion of 30 g potato protein do not differ from rates observed after ingesting an equivalent amount of milk protein.

Ingestion of Free Amino Acids Compared with an Equivalent Amount of Intact Protein Results in More Rapid Amino Acid Absorption and Greater Postprandial Plasma Amino Acid Availability Without Affecting Muscle Protein Synthesis Rates in Young Adults in a Double-Blind Randomized Trial

BackgroundThe rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates. ObjectiveWe sought to compare protein digestion, amino acid absorption kinetics, and the postprandial muscle protein synthetic response following ingestion of intact milk protein or an equivalent amount of free amino acids. MethodsTwenty-four healthy, young participants (mean ± SD age: 22 ± 3 y and BMI 23 ± 2 kg/m2; sex: 12 male and 12 female participants) received a primed continuous infusion of l-[ring-2H5]-phenylalanine and l-[ring-3,5–2H2]-tyrosine, after which they ingested either 30 g intrinsically l-[1–13C]-phenylalanine–labeled milk protein or an equivalent amount of free amino acids labeled with l-[1–13C]-phenylalanine. Blood samples and muscle biopsies were obtained to assess protein digestion and amino acid absorption kinetics (secondary outcome), whole-body protein net balance (secondary outcome), and mixed muscle protein synthesis rates (primary outcome) throughout the 6-h postprandial period. ResultsPostprandial plasma amino acid concentrations increased after ingestion of intact milk protein and free amino acids (both P < 0.001), with a greater increase following ingestion of the free amino acids than following ingestion of intact milk protein (P-time × treatment < 0.001). Exogenous phenylalanine release into plasma, assessed over the 6-h postprandial period, was greater with free amino acid ingestion (76 ± 9%) than with milk protein treatment (59 ± 10%; P < 0.001). Ingestion of free amino acids and intact milk protein increased mixed muscle protein synthesis rates (P-time < 0.001), with no differences between treatments (from 0.037 ± 0.015%/h to 0.053 ± 0.014%/h and 0.039 ± 0.016%/h to 0.051 ± 0.010%/h, respectively; P-time × treatment = 0.629). ConclusionsIngestion of a bolus of free amino acids leads to more rapid amino acid absorption and greater postprandial plasma amino acid availability than ingestion of an equivalent amount of intact milk protein. Ingestion of free amino acids may be preferred over ingestion of intact protein in conditions where protein digestion and amino acid absorption are compromised.

Basal protein synthesis rates differ between vastus lateralis and rectus abdominis muscle.

Background In vivo muscle protein synthesis rates are typically assessed by measuring the incorporation rate of stable isotope labelled amino acids in skeletal muscle tissue collected from vastus lateralis muscle. It remains to be established whether muscle protein synthesis rates in the vastus lateralis are representative of muscle protein synthesis rates of other muscle groups. We hypothesized that post‐absorptive muscle protein synthesis rates differ between vastus lateralis and rectus abdominis, pectoralis major, or temporalis muscle in vivo in humans.MethodsTwenty‐four patients (62 ± 3 years, 42% female), scheduled to undergo surgery, participated in this study and underwent primed continuous intravenous infusions with l‐[ring‐13C6]‐phenylalanine. During the surgical procedures, serum samples were collected, and muscle tissue was obtained from the vastus lateralis as well as from the rectus abdominis, pectoralis major, or temporalis muscle. Fractional mixed muscle protein synthesis rates (%/h) were assessed by measuring the incorporation of l‐[ring‐13C6]‐phenylalanine into muscle tissue protein.ResultsSerum l‐[ring‐13C6]‐phenylalanine enrichments did not change throughout the infusion period. Post‐absorptive muscle protein synthesis rates calculated based upon serum l‐[ring‐13C6]‐phenylalanine enrichments did not differ between vastus lateralis and rectus abdominis (0.032 ± 0.004 vs. 0.038 ± 0.003%/h), vastus lateralis and pectoralis major, (0.025 ± 0.003 vs. 0.022 ± 0.005%/h) or vastus lateralis and temporalis (0.047 ± 0.005 vs. 0.043 ± 0.005%/h) muscle, respectively (P > 0.05). When fractional muscle protein synthesis rates were calculated based upon tissue‐free l‐[ring‐13C6]‐phenylalanine enrichments as the preferred precursor pool, muscle protein synthesis rates were significantly higher in rectus abdominis (0.089 ± 0.008%/h) compared with vastus lateralis (0.054 ± 0.005%/h) muscle (P < 0.01). No differences were observed between fractional muscle protein synthesis rates in vastus lateralis and pectoralis major (0.046 ± 0.003 vs. 0.041 ± 0.008%/h) or vastus lateralis and temporalis (0.073 ± 0.008 vs. 0.083 ± 0.011%/h) muscle, respectively.ConclusionsPost‐absorptive muscle protein synthesis rates are higher in rectus abdominis when compared with vastus lateralis muscle. Post‐absorptive muscle protein synthesis rates do not differ between vastus lateralis and pectoralis major or temporalis muscle. Protein synthesis rates in muscle tissue samples obtained during surgery do not necessarily represent a good proxy for appendicular skeletal muscle protein synthesis rates.

Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults.

Purpose: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway.Methods: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C6] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis.Results: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects.Conclusions: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways.

Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement

Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement. Using l-[1,2-¹³C]leucine as a tracer, we measured the fractional synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins in 18 participants during sustained (7-h) insulin or saline infusion (n = 9 each). We also measured muscle ATP production, mitochondrial enzyme activities, mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins regulating protein synthesis. The concentration of circulating essential AA decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle PS rates were also lower during insulin (2-7 h) than during saline infusions despite increased mRNA levels of selected mitochondrial genes. Under these conditions, insulin did not alter mitochondrial enzyme activities and ATP production. These effects were associated with enhanced phosphorylation of Akt but not of protein synthesis activators mTOR, p70(S6K), and 4EBP1. In conclusion, sustained physiological hyperinsulinemia without AA replacement did not stimulate PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial ATP production in healthy humans. These results support that insulin and AA act in conjunction to stimulate muscle mitochondrial function and mitochondrial protein synthesis.

Protein Ingestion before Sleep Improves Postexercise Overnight Recovery

The role of nutrition in modulating postexercise overnight recovery remains to be elucidated. We assessed the effect of protein ingestion immediately before sleep on digestion and absorption kinetics and protein metabolism during overnight recovery from a single bout of resistance-type exercise. Sixteen healthy young males performed a single bout of resistance-type exercise in the evening (2000 h) after a full day of dietary standardization. All subjects were provided with appropriate recovery nutrition (20 g of protein, 60 g of CHO) immediately after exercise (2100 h). Thereafter, 30 min before sleep (2330 h), subjects ingested a beverage with (PRO) or without (PLA) 40 g of specifically produced intrinsically [1-C]phenylalanine-labeled casein protein. Continuous intravenous infusions with [ring-H5]phenylalanine and [ring-H2]tyrosine were applied with blood and muscle samples collected to assess protein digestion and absorption kinetics, whole-body protein balance and mixed muscle protein synthesis rates throughout the night (7.5 h). During sleep, casein protein was effectively digested and absorbed resulting in a rapid rise in circulating amino acid levels, which were sustained throughout the remainder of the night. Protein ingestion before sleep increased whole-body protein synthesis rates (311 ± 8 vs 246 ± 9 μmol·kg per 7.5 h) and improved net protein balance (61 ± 5 vs -11 ± 6 μmol·kg per 7.5 h) in the PRO vs the PLA experiment (P < 0.01). Mixed muscle protein synthesis rates were ∼22% higher in the PRO vs the PLA experiment, which reached borderline significance (0.059%·h ± 0.005%·h vs 0.048%·h ± 0.004%·h, P = 0.05). This is the first study to show that protein ingested immediately before sleep is effectively digested and absorbed, thereby stimulating muscle protein synthesis and improving whole-body protein balance during postexercise overnight recovery.

Neuromuscular electrical stimulation increases muscle protein synthesis rates in type 2 diabetic men

A loss of skeletal muscle proteins ultimately lowers the capacity for blood glucose disposal. Thus, the development of paradigms that can increase muscle protein accretion will have implications for the treatment of type 2 diabetes at a more advanced age. We aimed to determine the effect of neuromuscular electrical stimulation (NMES) on mixed muscle protein synthesis rates in type 2 diabetic men. Six sedentary, type 2 diabetic men (Age: 70±1 y, BMI: 26.5±1.0 kg·m−2) received a primed, constant infusion of L‐[ring‐13C6]phenylalanine and 60 min of one legged NMES. Biopsies of the vastus lateralis were obtained at 0, 2, and 4 h after NMES to measure mixed muscle protein synthesis rates in the unstimulated (CON) and stimulated (STIM) leg. The electrical current of the NMES protocol consisted of a pulse duration of 500 μs, pulse frequency of 60 Hz, and a 3 sec contraction – 3 sec relaxation time. Muscle protein synthesis rates were increased by 21% and 64% above CON at 0–2 h and 2–4 h in the STIM leg, respectively (P&lt;0.05). Similarly, the cumulative MPS response (0–4 h) was greater in the STIM (0.049±0.008 %·h−1) compared with the CON leg (0.039±0.008 %·h−1). Our data demonstrate that NMES stimulates mixed muscle protein synthesis rates in vivo in humans. This work lends credence to the use of NMES to attenuate muscle protein loss during periods of muscle disuse or to support an increase in skeletal muscle hypertrophy.

Skeletal Muscle DNA and Mixed Muscle Protein Synthesis Rates with Endurance Training in Aging Humans

Decreased rates of synthesis in skeletal muscle may contribute to loss of muscle mass with age. Acute studies show that resistance exercise can increase mixed muscle protein synthesis, an effect that is enhanced with protein consumption. However, less is known about the ability of endurance exercise training and protein consumption to promote synthetic processes. Deuterium oxide (D2O) consumption allows measurement of multiple synthetic processes and provides insight into skeletal muscle adaptations over extended periods. PURPOSE: The purpose of our study was to use D2O to determine long-term rates of protein, DNA and membrane phospholipid synthesis in skeletal muscle during endurance exercise training. METHODS: ixteen healthy adult males and females (Age: 50±8 yrs, BMI: 25.3±4.1 kg/m2, VO2 max: 28.3±6.4 ml/kg/min) participated in 6-weeks of endurance exercise training and were randomized to consume either carbohydrate (CHO) or an iso-caloric drink with 20-grams protein (PRO) following each session. Each participant also consumed D2O daily to determine the synthesis rate of proteins (MPS), DNA (DNA%F) and membrane phospholipid glycerol (GLY). VO2 max and muscle biopsies were performed pre and post training. Total muscle proteins, DNA and GLY were extracted from muscle biopsy samples and analyzed for deuterium enrichment using gas or liquid chromatography and mass spectrometry. RESULTS: he increase in VO2 max with training was greater in PRO compared to CHO (PRO=+12.8±6.2% vs. CHO=+2.8±8.7%, p=0.033). MPS was not different between PRO and CHO (PRO=0.05±0.01 vs. CHO=0.06±0.01 %/hr). DNA%F was not different between PRO and CHO (PRO=3.3±2.6 vs. CHO=5.3±2.8 % new in 6-weeks). MPS and DNA%F were correlated (r2=0.26, p=0.055). The synthesis of GLY was not different between PRO and CHO (PRO=37.6±11.9 vs. CHO=42.2±11.2 % new in 6-weeks). CONCLUSIONS: Our results suggest that protein consumption following each session of endurance exercise training can lead to long-term changes in aerobic capacity. MPS, DNA%F, or GLY had similar responses to training between PRO and CHO groups. The mean DNA%F of 4% is a novel measure of skeletal muscle DNA synthesis and cannot be accounted for by mitochondrial DNA turnover. These results may indicate satellite cell activation during endurance exercise training in aging adults.

Fiber Type‐Dependent Suppression of Myocellular Anabolic Response in the Obese Zucker Rat

The purpose of this study was to determine if insulin resistance syndrome is associated with a blunted myocellular anabolic response (e.g., cumulative protein synthesis rates [24‐h FSR]) following high‐intensity resistance exercise (RE). Lean (Fa/?) and obese (fa/fa) 5‐mo‐old male Zucker rats engaged in 4 sessions of lower body RE and were enriched with 2H2O to assess cumulative FSR in red (RG) and white gastrocnemius (WG). Obese Zucker rats exhibited a significantly higher basal 24‐h FSR in RG (+22%, P = 0.006) and WG (+ 38%, P = 0.026) compared to the lean phenotype, but were unable to augment protein synthesis rates in WG (−7%, P &gt; 0.05) to the same extent as lean rats (+34%, P = 0.027) following RE. Contrary to previous research, mixed muscle protein synthesis rates are enhanced rather than suppressed in selected muscle groups of the obese Zucker rat. Insulin resistance syndrome may impair the myocellular anabolic response following high‐intensity RE.

Co-ingestion of Protein and Leucine Stimulates Muscle Protein Synthesis in Young and Elderly Men

Aging is associated with a progressive loss of skeletal muscle mass, which is attributed to a disruption in the regulation of skeletal muscle protein turnover, which results in a chronic imbalance between muscle protein synthesis and breakdown rate. Knowledge of differences in responses of young and elderly subjects under normal daily living conditions are of crucial importance to our understanding of the etiology of sarcopenia and are currently lacking in the literature. PURPOSE: We investigated the response to the ingestion of carbohydrate with or without protein and free leucine following simulated activities of daily living (ADL) on whole-body protein balance and mixed muscle protein synthesis rates. METHODS: Eight elderly (75±1 y) and eight young (20±1 y) male subjects were randomly assigned to 2 trials in which they consumed either carbohydrate (CHO) or carbohydrate, protein and free leucine (CHO+PRO+leu) after performing 30 min of standardized ADL activities. Primed, continuous infusions with L-[ring−13C6]phenylalanine and L-[ring−2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover as well as fractional protein synthetic rate (FSR) in the vastus lateralis muscle over a 6 h period. RESULTS: Plasma insulin responses were significantly higher in the CHO+PRO+leu trial than in the CHO trial in both the young and elderly subjects (p<0.05). Whole-body phenylalanine and tyrosine fluxes were significantly higher in the young versus the elderly (p<0.01). Protein balance was negative in the CHO trial, but positive in the CHO+PRO+leu trial in both groups. In the CHO trial, muscle FSR was significantly lower in the elderly compared with the young subjects (p<0.05). Mixed muscle protein synthesis rates were significantly greater in the CHO+PRO+leu compared with the CHO trial in both the young (0.082±0.005%.h−1 vs. 0.060±0.005%h−1, respectively; p<0.01), and elderly subjects (0.072±0.006%h−1 vs. 0.043±0.003 %h−1 respectively; p<0.01), with no differences between groups. CONCLUSIONS: Co-ingestion of protein hydrolysate and leucine with carbohydrate following ADL activities improves whole-body protein balance and increases muscle protein synthesis rates to the same extent in young and elderly men.

Effect of aerobic exercise on age‐related decrease in muscle mitochondrial and sarcoplasmic protein synthesis

Whole body and mixed muscle protein synthesis rate declines with age in healthy people. In response to a 4-month aerobic exercise program we showed that mixed muscle protein synthesis rate increased 22%. Several gene transcripts that encode mitochondrial (mito) proteins increased in response to exercise but it remains to be determined whether these are translated to protein synthesis. In this study we tested the hypothesis that mito protein synthesis also increased in response to aerobic exercise training. Healthy men and women (N = 42) from 30–74 y were studied before and after a 4-month program of stationary bicycle training (3d/wk, up to 40min/d at 80% HRmax) or control activity. Muscle protein synthesis rate was measured using [15N] phenylalanine as a tracer. Mito and sarcoplasmic (sarco) proteins were separated from muscle biopsies for analysis. At baseline there was a decline with age (p<0.05) in both mito (6%/decade, r= −0.32) and sarco (5.5%/decade, r= −0.42) protein synthesis rate. Muscle protein synthesis rates did not change in control subjects, but in the exercise group mito synthesis increased 27% (0.046 ± 0.003 %/h pre vs. 0.058 ± 0.005 post, p=0.017, N=25) and there was a trend for 10% higher sarco protein synthesis (0.036 ± 0.002 %/h pre vs. 0.040 ± 0.003 post, p=0.066, N=33). These effects of exercise did not vary with age. We conclude that despite a decline in mito protein synthesis and function with advancing age, the potential for mito biogenesis in response to aerobic exercise remains robust in older muscle, as demonstrated by enhanced mito protein synthesis, gene expression, and enzyme action. Support: NIH RO1DK41973, MO1RR00585.

Myosin, sarcoplasmic and mitochondrial protein synthesis rates in rats adapted to a high protein diet

High protein diets have been shown to produce either no effect or a decrease in mixed muscle protein synthesis rates in rats and humans. However, no data regarding their effect on specific muscle protein fractions is available, despite their possible different metabolic regulation. In this context, we aimed at determining the fractional synthesis rates (FSR) of myosin, sarcoplasmic and mitochondrial protein fractions in gastrocnemius muscle of growing rats adapted to a high protein diet (HP, 49% of energy, n=16) for 14d or a normal protein diet (NP, 13% of energy, n=16). After the 14-d diets, rats were killed in the fasted or the fed state after a flooding dose of 13C-valine. NP and HP rats exhibited the same body weight, gastrocnemius mass, hydration and protein content. FSR and absolute synthesis rates of mixed muscle protein were neither significantly influenced by diet (NP or HP) nor by nutritional state (fasted or fed). There was also no effect of diet or nutritional state on the FSR of myosin fraction, sarcoplasmic or mitochondrial protein, which all ranged from 6 to 9%/d. Unlike splanchnic protein, which synthesis rates are greatly sensitive to an increased chronic protein intake, muscle protein fractions are not affected by dietary changes. This finding is in agreement with the lack of lean tissue anabolism usually accompanying high protein diets and suggest a very efficient system redistributing or oxidizing excess amino acids.

Insulin-like Growth Factor-1 Gene Transfer Augments Muscle Protein Synthesis Rate And Size In Adult Mice

Insulin-like growth factor I (IGF-I) is a potent myogenic factor that has been shown to play a critical role in muscle regeneration and muscle hypertrophy. Viral-mediated gene transfer of IGF-I upregulates muscle size and increases muscle strength. It is not clear whether IGF-I-induced muscle hypertrophy is mediated by an increase in protein synthesis and/or a decrease in proteolysis rates in existing myofibers and satellite cells. PURPOSE The objective of this study was to investigate the effect of IGF-I overexpression on in vivo muscle protein synthesis rate. METHODS The left hindlimb of young adult C57BL6 mice was injected with a recombinant adeno-associated virus vector for IGF-I (rAAV-1). The construct consisted of the entire rat IGF-I cDNA which encodes for IGF-I, a Myosin Light Chain (MLC) 1/3 promoter and enhancer, and SV40 polyadenlyation sequence. Six mice (age=3 weeks) were injected with 80ul of 10% glycerol/PBS containing approximately 1010 rAAV particles into the interstitial space of the anterior compartment of one hindlimb, targeting the extensor digitorum longus (EDL). Three months after transfection, in vivo mixed muscle protein synthesis rates were measured using the incorporation of intravenously administered L- [13C]-phe into EDL muscle proteins. [13C]-phe abundance in the structural proteins was quantitated using gas chromatography-combustion-isotope ratio mass spectrometry. Paired samples t-tests were used for comparisons between transfected and contralateral hindlimbs. RESULTS rAAV-IGF1 transfection resulted in a significant increase (mean ± SD) (12.1 ± 8.5%) in muscle wet weight and cross-sectional area (9.9 ± 9.1%)(p<0.05). In vivo mixed muscle protein synthesis rate was 26.9 ± 15.6% higher in the rAAV-IGF1 injected limbs compared to the contralateral control limb (p<0.05). Average EDL muscle protein synthesis rate was 10.5 ± 2.8%/day in the rAAV-IGF1 injected limb and 8.2 ± 1.9%/day in the contralateral limb. CONCLUSIONS These results demonstrate that muscle specific adeno-associated virus overexpression of IGF-I increased mixed muscle protein synthesis rate and this contributed to muscle hypertrophy. Further research will determine EDL contractile properties, and the components of the IGF-I signaling pathway that are activated in satellite cells and mature myofibers. Supported by R01-HD042955, NCRR-000954.

Reducing plasma HIV RNA improves muscle amino acid metabolism.

We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577-E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (> or =1 log) increased muscle protein synthesis rate and reduced R(a) Gln and muscle proteasome activity in 10 men and 1 woman (22-57 yr, 60-108 kg, 17-33 kg muscle) with advanced HIV (CD4 = 0-311 cells/microl; HIV RNA = 10-375 x 10(3) copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/microl, P = 0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P = 0.003). Mixed muscle protein synthesis rate increased (0.062 +/- 0.005 vs. 0.078 +/- 0.006%/h, P = 0.01), Ra Gln decreased (387 +/- 33 vs. 323 +/- 15 micromol.kg fat-free mass(-1).h(-1), P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% (P = 0.03). Muscle mass was only modestly increased (1 kg, P = not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, approximately 3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.

Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old.

Muscle atrophy (sarcopenia) in the elderly is associated with a reduced rate of muscle protein synthesis. The purpose of this study was to determine if weight-lifting exercise increases the rate of muscle protein synthesis in physically frail 76- to 92-yr-old women and men. Eight women and 4 men with mild to moderate physical frailty were enrolled in a 3-mo physical therapy program that was followed by 3 mo of supervised weight-lifting exercise. Supervised weight-lifting exercise was performed 3 days/wk at 65-100% of initial 1-repetition maximum on five upper and three lower body exercises. Compared with before resistance training, the in vivo incorporation rate of [(13)C]leucine into vastus lateralis muscle protein was increased after resistance training in women and men (P < 0.01), although it was unchanged in five 82 +/- 2-yr-old control subjects studied two times in 3 mo. Maximum voluntary knee extensor muscle torque production increased in the supervised resistance exercise group. These findings suggest that muscle contractile protein synthetic pathways in physically frail 76- to 92-yr-old women and men respond and adapt to the increased contractile activity associated with progressive resistance exercise training.

Increased plasma gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting.

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 Ra was 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 Ra in AIDS wasting exist.

Muscle protein turnover: methodological issues and the effect of aging.

Investigation of sarcopenia should include the measurement of muscle protein synthesis and breakdown because reduced muscle mass occurs only when muscle protein content is reduced. Protein content of a tissue is determined by the balance between synthesis and breakdown. Whole body measurements are inappropriate for determining the small changes in muscle protein synthesis and breakdown, since muscle contributes less than 30 percent to the whole body protein turnover. The measurement of mixed muscle protein synthesis in humans supports the animal data, which demonstrates that there is a decline in muscle protein synthesis with age. Resistance exercise stimulates mixed muscle protein synthesis rate in both the young and the old, although this is not demonstrated when myofibrillar protein synthesis is measured. Muscle is composed of several types of proteins, and their turnover may be differentially regulated. It is important, therefore, to measure the turnover of specific proteins such as myosin and actin, which are important contractile proteins. Recently, techniques have been developed to measure the synthesis rate of myosin heavy chain (MHC) in humans. In addition, the application of quantitative polymerase chain reaction (PCR) allows measurement of the steady state mRNA levels of various isoforms of MHC. These measurements, in combination with measurement of the synthesis rate of MHC, will allow us to understand the molecular regulation of specific proteins such as myosin. The important question is to determine whether the decline in muscle protein synthesis is genetically determined or secondary to inactivity, nutritional, hormonal, or other age-related alterations in body functions, and whether muscle wasting is reversible.(ABSTRACT TRUNCATED AT 250 WORDS)