Muscle Protein Synthesis In Response Research Articles

Attenuation of Resting but Not Load-Mediated Protein Synthesis in Prostate Cancer Patients on Androgen Deprivation.

Androgen deprivation therapy (ADT) is a common prostate cancer (PCa) treatment but results in muscular atrophy. Periodic increases in muscle protein synthesis (MPS) that occur after resistance exercise or protein intake may ameliorate this muscle loss, but the impact of these anabolic stimuli during ADT is unclear. To determine the acute MPS response to whey protein supplementation with and without resistance exercise during ADT. Acute response in PCa patients vs age-matched controls (CON). Academic laboratory setting. PCa patients on ADT (N = 8) and CON (N = 10). A standardized diet was consumed for 2 days prior to performing unilateral knee extension resistance exercise followed by ingestion of 40 g of whey protein. Bilateral biopsies and stable isotope infusions were used to determine MPS rates at rest after protein ingestion with and without resistance exercise. Baseline MPS during ADT was suppressed relative to CON (P = 0.01). Protein consumption stimulated MPS in both groups (approximate twofold increase, both P < 0.001), but to a greater extent in CON (P = 0.003). Protein plus resistance exercise increased MPS (∼3.4-fold increase, both P < 0.001) to a greater extent than did protein alone (P < 0.001), but with no difference between groups (P = 0.380). ADT reduces basal and protein feeding-induced rises in MPS; however, combined protein ingestion with resistance exercise stimulated MPS to a similar degree as CON. Testosterone appears to play a role in maintaining muscle mass but is not necessary to initiate a robust response in MPS following resistance exercise when combined with protein ingestion.

Leucine and Mammalian Target of Rapamycin–Dependent Activation of Muscle Protein Synthesis in Aging

The preservation or restoration of muscle mass is of prime importance for healthy aging. However, aging has been repeatedly shown to be associated with resistance of muscle to the anabolic effects of feeding. Leucine supplementation has been proposed as a possible strategy because of its regulatory role on protein homeostasis. Indeed, it acts independently of growth factors and leads to enhanced cap-dependent mRNA translation initiation and increased protein synthesis. Leucine acts as a signaling molecule directly at the muscle level via the activation of mammalian/mechanistic target of rapamycin complex 1 (mTORC1). However, in aged muscle, mTORC1 activation seems to be impaired, with decreased sensitivity and responsiveness of muscle protein synthesis to amino acids, whereas the phosphorylation state of several components of this signaling pathway appears to be higher in the basal state. This may stem from specific age-related impairment of muscle signaling and from decreased nutrient and growth factor delivery to the muscle. Whether aging per se affects mTORC1 signaling remains to be established, because aging is frequently associated with inadequate protein intake, decreased insulin sensitivity, inactivity, inflammatory processes, etc. Whatever its origin, this anabolic resistance to feeding can be mitigated by quantitative and qualitative manipulation of protein supply, such as leucine supplementation; however, there remains the question of possible adverse effects of long-term, high-dose leucine supplementation in terms of insulin resistance and tumorigenesis.

Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review.

The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesized and reported as providing sufficient or insufficient "evidence of age-related muscle anabolic resistance". Subsequently, three models were established to compare age-related differences in the MPS response to 1) exercise alone, 2) amino acid-based nutrition alone, or 3) the combination of exercise and amino acid-based nutrition. Following exercise alone, 8 of the 17 study arms provided sufficient evidence of age-related muscle anabolic resistance, while in response to amino acid-based nutrition alone, 8 of the 21 study arms provided sufficient evidence of age-related muscle anabolic resistance. When exercise and amino acid-based nutrition were combined, only 2 of the 10 study arms provided sufficient evidence of age-related muscle anabolic resistance. Our results highlight that optimization of exercise and amino acid-based nutrition is sufficient to induce a comparable MPS response between young and older individuals. However, the exercise volume completed and/or the amino acid/protein dose and leucine content must exceed a certain threshold to stimulate equivalent MPS rates in young and older adults, below which age-related muscle anabolic resistance may become apparent.

The response of muscle protein synthesis following whole‐body resistance exercise is greater following 40 g than 20 g of ingested whey protein

The currently accepted amount of protein required to achieve maximal stimulation of myofibrillar protein synthesis (MPS) following resistance exercise is 20–25 g. However, the influence of lean body mass (LBM) on the response of MPS to protein ingestion is unclear. Our aim was to assess the influence of LBM, both total and the amount activated during exercise, on the maximal response of MPS to ingestion of 20 or 40 g of whey protein following a bout of whole‐body resistance exercise. Resistance‐trained males were assigned to a group with lower LBM (≤65 kg; LLBM n = 15) or higher LBM (≥70 kg; HLBM n = 15) and participated in two trials in random order. MPS was measured with the infusion of 13C6‐phenylalanine tracer and collection of muscle biopsies following ingestion of either 20 or 40 g protein during recovery from a single bout of whole‐body resistance exercise. A similar response of MPS during exercise recovery was observed between LBM groups following protein ingestion (20 g – LLBM: 0.048 ± 0.018%·h−1; HLBM: 0.051 ± 0.014%·h−1; 40 g – LLBM: 0.059 ± 0.021%·h−1; HLBM: 0.059 ± 0.012%·h−1). Overall (groups combined), MPS was stimulated to a greater extent following ingestion of 40 g (0.059 ± 0.020%·h−1) compared with 20 g (0.049 ± 0.020%·h−1; P = 0.005) of protein. Our data indicate that ingestion of 40 g whey protein following whole‐body resistance exercise stimulates a greater MPS response than 20 g in young resistance‐trained men. However, with the current doses, the total amount of LBM does not seem to influence the response.

Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition

AbstractHealthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle “quality” decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies.

Effects of Whey, Caseinate, or Milk Protein Ingestion on Muscle Protein Synthesis after Exercise

Whey protein (WP) is characterized as a “fast” protein and caseinate (CA) as a “slow” protein according to their digestion and absorption rates. We hypothesized that co-ingestion of milk proteins (WP and CA) may be effective for prolonging the muscle protein synthesis response compared to either protein alone. We therefore compared the effect of ingesting milk protein (MP) to either WP or CA alone on muscle protein synthesis after exercise in rats. We also compared the effects of these milk-derived proteins to a control, soy protein (SP). Male Sprague-Dawley rats swam for two hours. Immediately after exercise, one of the following four solutions was administered: WP, CA, MP, or SP. Individual rats were euthanized at designated postprandial time points and triceps muscle samples collected for measurement of the protein fractional synthesis rate (FSR). FSR tended to increase in all groups post-ingestion, although the initial peaks of FSR occurred at different times (WP, peak time = 60 min, FSR = 7.76%/day; MP, peak time = 90 min, FSR = 8.34%/day; CA, peak time = 120 min, FSR = 7.85%/day). Milk-derived proteins caused significantly greater increases (p < 0.05) in FSR compared with SP at different times (WP, 60 min; MP, 90 and 120 min; CA, 120 min). Although statistical analysis could not be performed, the calculated the area under the curve (AUC) values for FSR following this trend were: MP, 534.61; CA, 498.22; WP, 473.46; and SP, 406.18. We conclude that ingestion of MP, CA or WP causes the initial peak time in muscle protein synthesis to occur at different times (WP, fast; MP, intermediate; CA, slow) and the dairy proteins have a superior effect on muscle protein synthesis after exercise compared with SP.

Cumulative Muscle Protein Synthesis and Protein Intake Requirements.

Muscle protein synthesis (MPS) fluctuates widely over the course of a day and is influenced by many factors. The time course of MPS responses to exercise and the influence of training and nutrition can only be pieced together from several different investigations and methods, many of which create unnatural experimental conditions. Measurements of cumulative MPS, the sum synthesis over an extended period, using deuterium oxide have been shown to accurately reflect muscle responses and may allow investigations of the response to exercise, total protein intake requirements, and interaction with protein timing in free-living experimental conditions; these factors have yet to be carefully integrated. Such studies could include clinical and athletic populations to integrate nutritional and exercise recommendations and help guide their revisions to optimize the skeletal muscle function that is so important to overall health.

Resistance Exercise Sustains p70S6K1 Activity in Response to Protein Ingestion at 4 hours

The additive effect of protein feeding and resistance exercise on the stimulation of muscle protein synthesis is well established. However, it is unclear whether the activity of the signalling protein p70S6K1 is enhanced when protein feeding is combined with resistance exercise compared with protein feeding alone. PURPOSE:To directly compare the response of p70S6K1 activity to protein feeding alone vs protein feeding combined with resistance exercise. METHODS:Retrospective signalling analysis was carried out on muscle tissue from a previously published study. Twenty-three resistance trained males consumed a high protein breakfast before resting for 3 h. Following a bout of unilateral resistance exercise (8 × 10 leg press and leg extension exercises; 80% 1 RM) participants consumed a whey protein isolate drink (containing 10, 20 or 40 g protein). The activity of p70S6K1 was measured at 0 and 4 h in rested and exercised legs using a [γ-32P] ATP kinase assay. Statistical analysis of the fold change (0-4 h) in p70S6K1 activity between rested and exercised legs was conducted using a paired samples t-test (protein doses were pooled). Linear regression analysis was performed on the difference in fold change of p70S6K1 between rested and exercised (x-axis) against the previously published myofibrillar muscle protein synthesis data (y-axis). Effect sizes were calculated and reported as Cohen’s d with confidence intervals (CI). RESULTS:The fold change in p70S6K1 activity in response to protein ingestion from 0-4 h was 62% higher (p=0.004; d=0.61; CI=0.14 to 1.08) in the exercised leg (1.8 ± 1.3 fold; mean ± SD) compared with the rested leg (1.1 ± 0.8 fold). Regression analysis revealed a significant linear relationship between the difference in p70S6K1 activity fold change between rested and exercised legs and previously published myofibrillar muscle protein synthesis data (p=0.031; r2=0.204; y=1.28+0.11*x). CONCLUSIONS: Resistance exercise enhances the response of p70S6K1 activity to protein feeding and likely contributes to the enhanced response of myofibrillar muscle protein synthesis when protein feeding and resistance exercise are combined. Partially funded by GSK Consumer Healthcare.

The impact of leucine‐enriched essential amino acid and whey protein dosing upon skeletal muscle protein synthesis in older women at rest and after exercise

Loss of skeletal muscle mass with ageing (sarcopenia) is a problem for which anabolic neutraceutical interventions could hold therapeutic promise. Older women are understudied with recommendations based on studies in older men inappropriate given that women exhibit distinct protein metabolism (i.e. reduced responses to feeding).We previously showed that increases in muscle protein synthesis (MPS) were identical in older women fed 3 g of 40% leucine‐enriched essential amino acids (LEAA) vs. 20 g whey protein (WP). Here we tested whether lower or higher doses of LEAA and WP modified this response.We recruited 24 older women (64±0.7 y) who received (N=8/group) 1.5 g LEAA, 6 g LEAA or 40 g WP while undergoing a primed constant I.V infusion of 13C6 phenylalanine. Using a unilateral resistance exercise model (6×8 leg extensions; 75% 1‐RM) we determined the effects of feeding (FED) and feeding‐plus‐exercise (FED‐EX) over a 2 and 4 h period upon MPS, microvascular blood flow (MBF) and plasma insulin. Muscle biopsies were taken from the vastus lateralis at baseline, 2.5 h later (BASAL) and then at 2 and 4 h in both the rest and exercised legs. MPS was determined by mass spectrometry, MBF by contrast‐enhanced ultrasound (CEUS) and plasma insulin by ELISA. Data were analyzed by 2‐way repeated measures ANOVA with Bonferroni post‐hoc testing; a P‐value of &lt;0.05 was considered significant.We found that FED increased MPS similarly in response to 1.5 g LEAA (0.061±0.003 vs. 0.086±0.005 %/h, P&lt;0.05), 6 g LEAA (0.066±0.006 vs. 0.090±0.007 %/h, P&lt;0.05) and 40 g WP (0.056±0.004 vs. 0.084±0.011 %/h, P&lt;0.01) over 0–2 h, whereas at 2–4 h this was not significantly different to baseline under each condition. Only 40g WP maintained FED responses at 0–4 h.At 0–2 h FED‐EX increased MPS only in response to 40 g WP (0.056±0.004 vs. 0.089±0.017 %/h, P&lt;0.05), however over 0–4 h increases in MPS were similar across the groups (1.5 g, 0.061±0.003 vs. 0.091±0.007 %/h, P&lt;0.01; 6 g, 0.066±0.006 vs. 0.097±0.007 %/h, P&lt;0.01 and 40 g WP, 0.56±0.004 vs. 0.104±0.011 %/h, P&lt;0.001).No significant increases in MBF were evident in response to FED, whilst only WP elicited increases with FED‐EX (0.13±0.04 vs. 0.31±0.09 AU, P&lt;0.05). Plasma insulin increased in response to 1.5 g LEAA (peak: 11.50±1.83 uU/mL), 6 g LEAA (peak: 12.76±1.61 uU/mL) and 40 g WP (peak: 21.03±3.62 uU/mL, all P&lt;0.01). However, both the peak and area under the curve (AUC: 74.62±11.8 vs. 45.6±10.4 (1.5 g LEAA), 33.79±3.0 (6 g LEAA), P&lt;0.05) was markedly greater in response to WP.We conclude there does not exist a bona fide dose‐response of MPS to FED in older women as 1.5 g of LEAA (equating to 0.6 g leucine and 0.9 g other EAA) maximally stimulated MPS in relation to 40 g WP. Similar was true following FED‐EX. The lack of increase in MBF is consistent with reports in older men while the heightened insulin response to WP vs. LEAA would not be expected to modify MPS given the permissive role of insulin in MPS. We conclude LEAA strategies have anabolic potential in older women; nonetheless longer‐term studies are needed to determine how “one‐off” MPS responses reflect myo‐anabolic and functional outcomes.Support or Funding InformationThis work was funded by Ajinomoto Company Incorporation

Selective Modulation of MicroRNA Expression with Protein Ingestion Following Concurrent Resistance and Endurance Exercise in Human Skeletal Muscle.

We examined changes in the expression of 13 selected skeletal muscle microRNAs (miRNAs) implicated in exercise adaptation responses following a single bout of concurrent exercise. In a randomized cross-over design, seven healthy males undertook a single trial consisting of resistance exercise (8 × 5 leg extension, 80% 1 Repetition Maximum) followed by cycling (30 min at ~70% VO2peak) with either post-exercise protein (PRO: 25 g whey protein) or placebo (PLA) ingestion. Muscle biopsies (vastus lateralis) were obtained at rest and 4 h post-exercise. Detection of miRNA via quantitative Polymerase Chain Reaction (qPCR) revealed post-exercise increases in miR-23a-3p (~90%), miR-23b-3p (~39%), miR-133b (~80%), miR-181-5p (~50%), and miR-378-5p (~41%) at 4 h post-exercise with PRO that also resulted in higher abundance compared to PLA (P < 0.05). There was a post-exercise decrease in miR-494-3p abundance in PLA only (~88%, P < 0.05). There were no changes in the total abundance of target proteins post-exercise or between conditions. Protein ingestion following concurrent exercise can modulate the expression of miRNAs implicated in exercise adaptations compared to placebo. The selective modulation of miRNAs with target proteins that may prioritize myogenic compared to oxidative/metabolic adaptive responses indicate that miRNAs can play a regulatory role in the molecular machinery enhancing muscle protein synthesis responses with protein ingestion following concurrent exercise.

Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men.

Fish oil (FO) supplementation potentiates muscle protein synthesis (MPS) in response to a hyperaminoacidemic–hyperinsulinemic infusion. Whether FO supplementation potentiates MPS in response to protein ingestion or when protein ingestion is combined with resistance exercise (RE) remains unknown. In a randomized, parallel group design, 20 healthy males were randomized to receive 5 g/day of either FO or coconut oil control (CO) for 8 weeks. After supplementation, participants performed a bout of unilateral RE followed by ingestion of 30 g of whey protein. Skeletal muscle biopsies were obtained before and after supplementation for assessment of muscle lipid composition and relevant protein kinase activities. Infusion of l‐[ring‐13C6] phenylalanine was used to measure basal myofibrillar MPS at rest (REST), in a nonexercised leg following protein ingestion (FED) and following RE and protein ingestion (FEDEX). MPS was significantly elevated above REST during FEDEX in both the FO and CO groups, but there was no effect of supplementation. There was a significant increase in MPS in both groups above REST during FED but no effect of supplementation. Supplementation significantly decreased panPKB activity at REST in the FO group but not the CO group. There was a significant increase from REST at post‐RE for PKB and AMPK α2 activity in the CO group but not in the FO group. In FEDEX, there was a significant increase in p70S6K1 activity from REST at 3 h in the CO group only. These data highlight that 8 weeks of FO supplementation alters kinase signaling activity in response to RE plus protein ingestion without influencing MPS.

What is the Optimal Amount of Protein to Support Post-Exercise Skeletal Muscle Reconditioning in the Older Adult?

Hyperaminoacidemia following protein ingestion enhances the anabolic effect of resistance-type exercise by increasing the stimulation of muscle protein synthesis and attenuating the exercise-mediated increase in muscle protein breakdown rates. Although factors such as the source of protein ingested and the timing of intake relative to exercise can impact post-exercise muscle protein synthesis rates, the amount of protein ingested after exercise appears to be the key nutritional factor dictating the magnitude of the muscle protein synthetic response during post-exercise recovery. In younger adults, muscle protein synthesis rates after resistance-type exercise respond in a dose-dependent manner to ingested protein and are maximally stimulated following ingestion of ~20g of protein. In contrast to younger adults, older adults are less sensitive to smaller doses of ingested protein (less than ~20g) after exercise, as evidenced by an attenuated increase in muscle protein synthesis rates during post-exercise recovery. However, older muscle appears to retain the capacity to display a robust stimulation of muscle protein synthesis in response to the ingestion of greater doses of protein (~40g), and such an amount may be required for older adults to achieve a robust stimulation of muscle protein synthesis during post-exercise recovery. The aim of this article is to discuss the current state of evidence regarding the dose-dependent relationship between dietary protein ingestion and changes in skeletal muscle protein synthesis during recovery from resistance-type exercise in older adults. We provide recommendations on the amount of protein that may be required to maximize skeletal muscle reconditioning in response to resistance-type exercise in older adults.

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men.

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis.

We aimed to investigate the role of insulin in regulating human skeletal muscle metabolism in health and diabetes. We conducted a systematic review and meta-analysis of published data that examined changes in skeletal muscle protein synthesis (MPS) and/or muscle protein breakdown (MPB) in response to insulin infusion. Random-effects models were used to calculate weighted mean differences (WMDs), 95% CIs and corresponding p values. Both MPS and MPB are reported in units of nmol (100ml leg vol.)(-1) min(-1). A total of 104 articles were examined in detail. Of these, 44 and 25 studies (including a total of 173 individuals) were included in the systematic review and meta-analysis, respectively. In the overall estimate, insulin did not affect MPS (WMD 3.90 [95% CI -0.74, 8.55], p = 0.71), but significantly reduced MPB (WMD -15.46 [95% CI -19.74, -11.18], p < 0.001). Overall, insulin significantly increased net balance protein acquisition (WMD 20.09 [95% CI 15.93, 24.26], p < 0.001). Subgroup analysis of the effect of insulin on MPS according to amino acid (AA) delivery was performed using meta-regression analysis. The estimate size (WMD) was significantly different between subgroups based on AA availability (p = 0.001). An increase in MPS was observed when AA availability increased (WMD 13.44 [95% CI 4.07, 22.81], p < 0.01), but not when AA availability was reduced or unchanged. In individuals with diabetes and in the presence of maintained delivery of AA, there was a significant reduction in MPS in response to insulin (WMD -6.67 [95% CI -12.29, -0.66], p < 0.05). This study demonstrates the complex role of insulin in regulating skeletal muscle metabolism. Insulin appears to have a permissive role in MPS in the presence of elevated AAs, and plays a clear role in reducing MPB independent of AA availability.

Resistance exercise training and circulatory responses to feeding and skeletal muscle protein anabolism in older men.

Sarcopenia, the age-related loss of muscle mass, contributes to frailty and the loss of independence in older adults. It is well known that ageing results in a decreased sensitivity of skeletal muscle to the anabolic effects of dietary protein, and one explanation for this may be the age-related reduction in muscle leg blood flow and microvascular blood volume (MBV). Low MBV could compromise the postprandial transport of key amino acids and insulin to skeletal muscle where they are known to stimulate muscle protein synthesis (MPS) and arrest rates of muscle protein breakdown (MPB), respectively. As a result, strategies that enhance MBV in older adults may augment the delivery of amino acids and insulin to skeletal muscle following a meal and thus serve as a viable means to combat sarcopenia.

Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function.

Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ± 1.1 kg · m(-2)) and 15 healthy-weight (BMI 23.4 ± 0.3 kg · m(-2)) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under postabsorptive (hypoinsulinemic-euglycemic clamp) and postprandial (hyperinsulinemic hyperaminoacidemic-euglycemic clamp) conditions. Obesity was associated with systemic inflammation, greater leg fat mass, and patterns of mRNA expression consistent with muscle deconditioning, whereas leg lean mass, strength, and work done during maximal exercise were no different. Under postabsorptive conditions, MPS and LPB were equivalent between groups, whereas insulin and amino acid administration increased MPS in only healthy-weight subjects and was associated with lower leg glucose disposal (LGD) (63%) in obese men. Blunting of MPS in the obese men was offset by an apparent decline in LPB, which was absent in healthy-weight subjects. Lower postprandial LGD in obese subjects and blunting of MPS responses to amino acids suggest that obesity in older adults is associated with diminished muscle metabolic quality. This does not, however, appear to be associated with lower leg lean mass or strength.

Nutrient-Induced Stimulation of Protein Synthesis in Mouse Skeletal Muscle Is Limited by the mTORC1 Repressor REDD11–3

In skeletal muscle, the nutrient-induced stimulation of protein synthesis requires signaling through the mechanistic target of rapamycin complex 1 (mTORC1). Expression of the repressor of mTORC1 signaling, regulated in development and DNA damage 1 (REDD1), is elevated in muscle during various atrophic conditions and diminished under hypertrophic conditions. The question arises as to what extent REDD1 limits the nutrient-induced stimulation of protein synthesis. The objective was to examine the role of REDD1 in limiting the response of muscle protein synthesis and mTORC1 signaling to a nutrient stimulus. Wild type REDD1 gene (REDD1(+/+)) and disruption in the REDD1 gene (REDD1(-/-)) mice were feed deprived for 16 h and randomized to remain feed deprived or refed for 15 or 60 min. The tibialis anterior was then removed for analysis of protein synthesis and mTORC1 signaling. In feed-deprived mice, protein synthesis and mTORC1 signaling were significantly lower in REDD1(+/+) than in REDD1(-/-) mice. Thirty minutes after the start of refeeding, protein synthesis in REDD1(+/+) mice was stimulated by 28%, reaching a value similar to that observed in feed-deprived REDD1(-/-) mice, and was accompanied by increased phosphorylation of mTOR (Ser2448), p70S6K1 (Thr389), and 4E-BP1 (Ser65) by 81%, 167%, and 207%, respectively. In refed REDD1(-/-) mice, phosphorylation of mTOR (Ser2448), p70S6K1 (Thr389), and 4E-BP1 (Ser65) were significantly augmented above the values observed in refed REDD1(+/+) mice by 258%, 405%, and 401%, respectively, although protein synthesis was not coordinately increased. Seventy-five minutes after refeeding, REDD1 expression in REDD1(+/+) mice was reduced (∼15% of feed-deprived REDD1(+/+) values), and protein synthesis and mTORC1 signaling were not different between refed REDD1(+/+) mice and REDD1(-/-) mice. The results show that REDD1 expression limits protein synthesis in mouse skeletal muscle by inhibiting mTORC1 signaling during periods of feed deprivation and that a reduction in its expression is necessary for maximal stimulation of protein synthesis in response to refeeding.

Delayed Activation of Muscle Protein Synthesis following Resistance Exercise in Mice is mTORC1‐Dependent

The activation of the mechanistic target of rapamycin-complex-1 (mTORC1) is important for muscle hypertrophy following resistance exercise. However, our present understanding of the dynamics of anabolic signaling and muscle protein synthesis (MPS) following an acute bout of resistance exercise in mice is lacking. PURPOSE: To determine the time course of anabolic signaling and MPS in response to an acute bout of resistance exercise in mice. METHODS: Three month old C57BL/6 mice (n = 56) were anesthetized, the sciatic nerve exposed before the point of trifurcation, and all of the muscles of the right distal hindlimb were stimulated for 10 sets of 6 repetitions with 1 minute rest between sets. Both control and stimulated tibialis anterior (TA) muscles were collected 0, 0.75, 1.5, 3, 4.5, 6, 9, 12 and 24 hours post-loading. Thirty minutes prior to collection animals were injected with 100 μL of 0.04 μmol/g puromycin. Two additional groups of mice were injected with 110 μL of 1.5 μg/g rapamycin or saline immediately prior to loading and collected 6h later. Muscles were processed for western blot analysis of proposed anabolic signaling molecules and MPS via SUnSET. RESULTS: ERK1/2 phosphorylation peaked at 0.75h (2.76 ± 0.60) and pS6K1 Thr389 was significantly higher 1.5h (4.18 ± 2.75) and 3h (5.39 ± 0.62) post-loading (p < 0.05). MPS showed two peaks, the first at 0.75h (1.27 ± 0.14) and the second at 6h (1.27 ± 0.10) post-loading. Rapamycin abolished the peak at 6h even though mTORC1 activity was not elevated at this timepoint. CONCLUSION Following acute resistance exercise in mice, there are two peaks of anabolic activity. The first corresponds with an increase in ERK1/2 activity 0.75h after loading and the second, at 6h, is dependent on mTORC1 activation.

The Effect of Soy‐Dairy Protein Blend Supplementation during Resistance Exercise Training

Soy‐dairy protein blend (PB) ingestion prolongs the muscle protein synthesis response to a bout of resistance exercise. The efficacy of PB supplementation with resistance exercise training (RET) has not been evaluated in chronic studies. Our aim was to determine the effect of PB supplementation during RET on lean body mass (LBM), muscle thickness and strength. Healthy young men participated in supervised whole body progressive RET at 60‐80% 1 maximum (1‐RM), 3d/wk for 3 months. Participants were randomized to one of three treatments to ingest 22g protein as soy‐dairy protein blend (PB, N=23), whey protein isolate (WP, N=22) or an isocaloric placebo, 22g maltodextrin (MP, N=23) daily. Whole body lean mass (LBM), muscle strength (dynamometry &amp; 1‐&amp; 8‐RM testing) and vastus lateralis muscle thickness (MT) were assessed at pre &amp; post RET. All treatments increased LBM (p&lt;0.05). PB exhibited a trend for greater LBM change compared to MP (0.92 kg: ‐0.12, 1.95); however, there was no difference in LBM change between WP &amp; MP. Muscle strength (RM tested) and thickness increased similarly for all treatments. All treatments increased isometric knee extension and flexion torque (P&lt;0.05). Both protein‐supplemented treatments increased isokinetic knee extension torque (P&lt;0.05). In conclusion, a soy‐dairy protein blend may enhance LBM during a 3 month RET period, and minor differences in strength between treatments were observed.

A review of resistance training-induced changes in skeletal muscle protein synthesis and their contribution to hypertrophy.

Muscle protein synthesis (MPS) is stimulated by resistance exercise (RE) and is further stimulated by protein ingestion. The summation of periods of RE-induced increases in MPS can induce hypertrophy chronically. As such, studying the response of MPS with resistance training (RT) is informative, as adaptations in this process can modulate muscle mass gain. Previous studies have shown that the amplitude and duration of increases in MPS after an acute bout of RE are modulated by an individual's training status. Nevertheless, it has been shown that the initial responses of MPS to RE and nutrition are not correlated with subsequent hypertrophy. Thus, early acute responses of MPS in the hours after RE, in an untrained state, do not capture how MPS can affect RE-induced muscle hypertrophy. The purpose of this review is provide an in-depth understanding of the dynamic process of muscle hypertrophy throughout RT by examining all of the available data on MPS after RE and in different phases of an RT programme. Analysis of the time course and the overall response of MPS is critical to determine the potential protein accretion after an RE bout. Exercise-induced increases in MPS are shorter lived and peak earlier in the trained state than in the untrained state, resulting in a smaller overall muscle protein synthetic response in the trained state. Thus, RT induces a dampening of the MPS response, potentially limiting protein accretion, but when this occurs remains unknown.