Muscle Myofibrillar Protein Synthesis Research Articles

Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery.

Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer. Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling. OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day-1, p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160Thr642 (p = 0.046) post-HIIT. A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).

Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a \u2018Combined Oral Stable Isotope Assessment of Muscle (COSIAM)\u2019 approach

Optimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits the applicability of these approaches in certain populations (e.g. clinical, frail elderly). To concurrently quantify skeletal muscle mass and muscle protein turnover i.e. muscle protein synthesis (MPS) and muscle protein breakdown (MPB), in elderly human volunteers using stable-isotope labelled tracers i.e. Methyl-[D3]-creatine (D3-Cr), deuterium oxide (D2O), and Methyl-[D3]-3-methylhistidine (D3-3MH), to measure muscle mass, MPS and MPB, respectively. We recruited 10 older males (71 ± 4 y, BMI: 25 ± 4 kg.m2, mean ± SD) into a 4-day study, with DXA and consumption of D2O and D3-Cr tracers on day 1. D3-3MH was consumed on day 3, 24 h prior to returning to the lab. From urine, saliva and blood samples, and a single muscle biopsy (vastus lateralis), we determined muscle mass, MPS and MPB. D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r = 0.69, P = 0.027). Rates of cumulative myofibrillar MPS over 3 days were 0.072%/h (95% CI, 0.064 to 0.081%/h). Whole-body MPB over 6 h was 0.052 (95% CI, 0.038 to 0.067). These rates were similar to previous literature. We demonstrate the potential for D3-Cr to be used alongside D2O and D3-3MH for concurrent measurement of muscle mass, MPS, and MPB using a minimally invasive design, applicable for clinical and frail populations.

Does Muscle Hypertrophy Relate To Resistance Training-Induced Changes In Myofibrillar Protein Synthesis In Women?

Resistance exercise (RE) elevates skeletal muscle myofibrillar protein synthesis (MyoPS) for up to 48h, which can be measured under ‘free-living’ conditions using deuterium oxide (D2O). The accumulation of repeated bouts of RE (resistance training—RT) results in skeletal muscle hypertrophy, which in men has been reported to correlate with post-RE ‘free-living’ MyoPS only in the trained state. However, the impact of training status on acute responses to RE and their relationship to hypertrophic adaptations has yet to be investigated in women. PURPOSE: The present study examined the MyoPS response over 48h of recovery from an acute bout of RE in the untrained (UT) and trained (T) state to determine its association with hypertrophic adaptations in women. METHODS: Ten recreationally active young women (23±5 yr, 62.3±12.0 kg, 23.7±7.4 % body fat; mean±SD) underwent ~8 wk of supervised whole-body RT (4 x 10 repetitions, 75% 1 repetition maximum (1RM), 3x/wk). Whole-body fat free mass (FFM; BODPOD), vastus lateralis muscle thickness (MT; B-mode ultrasound) and 1RM for each completed exercise were measured in the UT and T state to quantify training responses. MyoPS was measured during the mid-follicular phase (day 3-9 of the menstrual cycle) at rest pre-training and for 48h following the first and final bout of RE using orally administered D2O. Muscle biopsies were obtained at pre-RE (0h), 24h and 48h post-RE to determine MyoPS in both the UT and T state. RESULTS: Following RT, there was a ~3.4% increase in FFM (49.3±6.4 vs. 51.0±6.9 kg; P < 0.001) and ~8.8% increase in MT (2.31±0.39 vs. 2.50±0.38 cm; P < 0.05). Representative 1RM strength increased for bench press and leg press exercise (28.5±5.8 kg vs. 38.7±9.8 kg and 151.6±63.5 vs. 259.3±92.7 kg, respectively; P < 0.01). Forthcoming analysis will determine if: i) training alters the post-exercise MyoPS response, and; ii) whether muscle hypertrophy correlates with acute MyoPS in the UT and/or T state. CONCLUSIONS: Women responded favourably to ~8 wk of RT with significant gains in FFM, MT and 1RM strength. Ongoing analysis will provide insight into the potential relationship between acute muscle protein synthesis and training-induced hypertrophy in the understudied female population. Supported by the Natural Sciences and Engineering Research Council of Canada.

Potato Protein Stimulates Muscle Protein Synthesis At Rest And With Resistance Exercise

Skeletal muscle protein synthesis (MPS) is increased in response to amino acid feeding and to resistance exercise (RE) where RE enhances MPS above feeding alone. The use of vegetable based proteins have increased in popularity, however many vegetable based protein sources are of lower protein quality. Potato protein (PP) is a complete protein and has the highest protein quality score of any vegetable protein, however, its efficacy in stimulating MPS beyond the acute setting has yet to be determined. PURPOSE: To determine the effects of PP on MPS with and without RE in healthy young women. METHODS: In a single blind, parallel-group design, twenty-four healthy younger women (21 ± 3 years, n = 12/group) were assigned to consume either 25 g of PP twice daily or a non-protein-containing control (CON). Participants consumed a fully controlled diet for 3 weeks (0.8 g/kg/day CON, 1.6 g/kg/day PP), with non-supplemental protein comprising 51 ± 3% of total protein intake in the PP group. One leg of each participant was randomly allocated to perform RE (Exercise) while the other leg served as a rested control (Rest). RE was performed thrice weekly at ~30% of 1RM (20-25 reps) for 3 sets until volitional fatigue on the leg extension and leg press machines. Myofibrillar MPS was measured at baseline, following supplementation, and at supplementation+RE via the deuterated water method. RESULTS: PP ingestion increased MPS by 0.14 ± 0.09 %/d at Rest and by 0.32 ± 0.14 %/d in Exercise (p = 0.008) while MPS was elevated only in Exercise with CON 0.20 ± 0.11 %/d but was not different from Baseline 0.01 ± 0.04. CONCLUSIONS: Consuming PP in addition to a habitual diet increased rates of MPS at rest and there was a further increase with RE. PP may serve as a high quality, vegetable-based protein supplement to augment muscle protein anabolism in healthy young women. Support by The Alliance for Potato Research & Education

Effects of Prolonged Energy Restriction and Dietary Protein on Muscle Protein Synthesis and Proteome Dynamics in Obese Zucker Rats

Abstract Objectives High protein (HP) diets during short-term energy restriction (ER) attenuate energy-mediated reductions in muscle protein synthesis (MPS). MPS-adaptive responses to HP diets during prolonged ER are not well described. This study examined the effects of prolonged ER and HP on MPS and the synthesis rates of numerous individual muscle proteins. Methods Female 6-wk-old obese Zucker (leprfa+/fa+, n = 48) rats were randomized to one of four diet groups for 10 weeks: ad libitum-standard protein (AL-SP; 14% protein), AL-HP (35% protein), ER-SP, and ER-HP (both fed 60% of intake of AL-SP). At the start of week 10, D2O was administered by intraperitoneal injection and isotopic equilibrium was maintained daily by providing D2O in drinking water. Rats were euthanized after 1 week of labeling, and mixed-MPS (gastrocnemius), absolute mixed-MPS (mixed-MPS x muscle protein content), proteome dynamics, and protein half-lives [rate/d (k) = –ln(1-f)/d, where f is mixed-MPS and t is time in days; t1/2 (days) = ln(2)/k] were quantified. Results Mixed-MPS was not altered by energy status and protein intake. Gastrocnemius mass was lower (P &amp;lt; 0.001) in ER-fed rats than AL-fed rats and higher (P = 0.034) for AL-HP than AL-SP. As a result, absolute mixed-MPS was lower (P &amp;lt; 0.005) in ER than AL, regardless of dietary protein. Absolute synthesis in 24 of 26 myofibrillar, 32 of 61 mitochondrial, and 55 of 60 cytoplasmic measured proteins were lower in ER than AL (P &amp;lt; 0.05), regardless of dietary protein. The difference in absolute synthesis of myofibrillar, mitochondrial, and cytoplasmic proteins due to ER compared to AL was 28%, 16%, and 27%, respectively. Comparison of HP and SP within each energy state revealed lower turnover rates and prolonged half-lives for a majority of measured muscle proteins in HP than in SP in both ER and AL conditions (P &amp;lt; 0.001). Conclusions Prolonged ER in obese Zucker rats exerted a strong suppressive effect on myofibrillar, mitochondrial, and cytoplasmic MPS, suggesting reduced protein accretion contributed to lower gastrocnemius mass in ER-fed rats. Lower turnover rates of most muscle proteins in HP-fed rats without reductions in protein pool size (i.e., tissue mass) suggests prolonged HP intake, independent of energy, may prolong muscle protein lifespan of in obese Zucker rats. Funding Sources Supported by USAMRDC; authors’ views not official U.S. Army or DoD policy.

Potato Protein Isolate Stimulates Muscle Protein Synthesis at Rest and with Resistance Exercise in Young Women.

Skeletal muscle myofibrillar protein synthesis (MPS) increases in response to protein feeding and to resistance exercise (RE), where each stimuli acts synergistically when combined. The efficacy of plant proteins such as potato protein (PP) isolate to stimulate MPS is unknown. We aimed to determine the effects of PP ingestion on daily MPS with and without RE in healthy women. In a single blind, parallel-group design, 24 young women (21 ± 3 years, n = 12/group) consumed a weight-maintaining baseline diet containing 0.8 g/kg/d of protein before being randomized to consume either 25 g of PP twice daily (1.6 g/kg/d total protein) or a control diet (CON) (0.8 g/kg/d total protein) for 2 wks. Unilateral RE (~30% of maximal strength to failure) was performed thrice weekly with the opposite limb serving as a non-exercised control (Rest). MPS was measured by deuterated water ingestion at baseline, following supplementation (Rest), and following supplementation + RE (Exercise). Ingestion of PP stimulated MPS by 0.14 ± 0.09 %/d at Rest, and by 0.32 ± 0.14 %/d in the Exercise limb. MPS was significantly elevated by 0.20 ± 0.11 %/d in the Exercise limb in CON (p = 0.008). Consuming PP to increase protein intake to levels twice the recommended dietary allowance for protein augmented rates of MPS. Performance of RE stimulated MPS regardless of protein intake. PP is a high-quality, plant-based protein supplement that augments MPS at rest and following RE in healthy young women.

The Effects Potato Protein on Rates of Myofibrillar Muscle Protein Synthesis in Young Women

The Effects Potato Protein on Rates of Myofibrillar Muscle Protein Synthesis in Young Women

Six Weeks of Low-Load Blood Flow Restricted and High-Load Resistance Exercise Training Produce Similar Increases in Cumulative Myofibrillar Protein Synthesis and Ribosomal Biogenesis in Healthy Males.

Purpose: High-load resistance exercise contributes to maintenance of muscle mass, muscle protein quality, and contractile function by stimulation of muscle protein synthesis (MPS), hypertrophy, and strength gains. However, high loading may not be feasible in several clinical populations. Low-load blood flow restricted resistance exercise (BFRRE) may provide an alternative approach. However, the long-term protein synthetic response to BFRRE is unknown and the myocellular adaptations to prolonged BFRRE are not well described.Methods: To investigate this, 34 healthy young subjects were randomized to 6 weeks of low-load BFRRE, HLRE, or non-exercise control (CON). Deuterium oxide (D2O) was orally administered throughout the intervention period. Muscle biopsies from m. vastus lateralis were collected before and after the 6-week intervention period to assess long-term myofibrillar MPS and RNA synthesis as well as muscle fiber-type-specific cross-sectional area (CSA), satellite cell content, and myonuclei content. Muscle biopsies were also collected in the immediate hours following single-bout exercise to assess signaling for muscle protein degradation. Isometric and dynamic quadriceps muscle strength was evaluated before and after the intervention.Results: Myofibrillar MPS was higher in BFRRE (1.34%/day, p < 0.01) and HLRE (1.12%/day, p < 0.05) compared to CON (0.96%/day) with no significant differences between exercise groups. Muscle RNA synthesis was higher in BFRRE (0.65%/day, p < 0.001) and HLRE (0.55%/day, p < 0.01) compared to CON (0.38%/day) and both training groups increased RNA content, indicating ribosomal biogenesis in response to exercise. BFRRE and HLRE both activated muscle degradation signaling. Muscle strength increased 6–10% in BFRRE (p < 0.05) and 13–23% in HLRE (p < 0.01). Dynamic muscle strength increased to a greater extent in HLRE (p < 0.05). No changes in type I and type II muscle fiber-type-specific CSA, satellite cell content, or myonuclei content were observed.Conclusions: These results demonstrate that BFRRE increases long-term muscle protein turnover, ribosomal biogenesis, and muscle strength to a similar degree as HLRE. These findings emphasize the potential application of low-load BFRRE to stimulate muscle protein turnover and increase muscle function in clinical populations where high loading is untenable.

Impact of dairy protein during limb immobilization and recovery on muscle size and protein synthesis; a randomized controlled trial.

Muscle disuse results in the loss of muscular strength and size, due to an imbalance between protein synthesis (MPS) and breakdown (MPB). Protein ingestion stimulates MPS, although it is not established if protein is able to attenuate muscle loss with immobilization (IM) or influence the recovery consisting of ambulatory movement followed by resistance training (RT). Thirty men (49.9 ± 0.6 yr) underwent 14 days of unilateral leg IM, 14 days of ambulatory recovery (AR), and a further six RT sessions over 14 days. Participants were randomized to consume an additional 20 g of dairy protein or placebo with a meal during the intervention. Isometric knee extension strength was reduced following IM (-24.7 ± 2.7%), partially recovered with AR (-8.6 ± 2.6%), and fully recovered after RT (-0.6 ± 3.4%), with no effect of supplementation. Thigh muscle cross-sectional area decreased with IM (-4.1 ± 0.5%), partially recovered with AR (-2.1 ± 0.5%), and increased above baseline with RT (+2.2 ± 0.5%), with no treatment effect. Myofibrillar MPS, measured using deuterated water, was unaltered by IM, with no effect of protein. During AR, MPS was increased only with protein supplementation. Protein supplementation did not attenuate the loss of muscle size and function with disuse or potentiate recovery but enhanced myofibrillar MPS during AR. NEW & NOTEWORTHY Twenty grams of daily protein supplementation does not attenuate the loss of muscle size and function induced by 2 wk of muscle disuse or potentiate recovery in middle-age men. Average mitochondrial but not myofibrillar muscle protein synthesis was attenuated during immobilization with no effect of supplementation. Protein supplementation increased myofibrillar protein synthesis during a 2-wk period of ambulatory recovery following disuse but without group differences in phenotype recovery.

Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis following Resistance Exercise in Humans.

The ingestion of intact protein or essential amino acids (EAA) stimulates mechanistic target of rapamycin complex-1 (mTORC1) signaling and muscle protein synthesis (MPS) following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs) only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients) following resistance exercise in humans. Ten young (20.1 ± 1.3 years), resistance-trained men completed two trials, ingesting either 5.6 g BCAA or a placebo (PLA) drink immediately after resistance exercise. Myofibrillar-MPS was measured during exercise recovery with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre and 4 h-post drink ingestion. Blood samples were collected at time-points before and after drink ingestion. Western blotting was used to measure the phosphorylation status of mTORC1 signaling proteins in biopsies collected pre, 1-, and 4 h-post drink. The percentage increase from baseline in plasma leucine (300 ± 96%), isoleucine (300 ± 88%), and valine (144 ± 59%) concentrations peaked 0.5 h-post drink in BCAA. A greater phosphorylation status of S6K1Thr389 (P = 0.017) and PRAS40 (P = 0.037) was observed in BCAA than PLA at 1 h-post drink ingestion. Myofibrillar-MPS was 22% higher (P = 0.012) in BCAA (0.110 ± 0.009%/h) than PLA (0.090 ± 0.006%/h). Phenylalanine Ra was ~6% lower in BCAA (18.00 ± 4.31 μmol·kgBM−1) than PLA (21.75 ± 4.89 μmol·kgBM−1; P = 0.028) after drink ingestion. We conclude that ingesting BCAAs alone increases the post-exercise stimulation of myofibrillar-MPS and phosphorylation status mTORC1 signaling.

A Lower Protein Leucine‐matched Beverage Induces Similar Increases in Acute and Integrated Muscle Protein Synthesis in Healthy Older Women

Sarcopenic muscle and strength loss negatively impact health. Sarcopenic muscle loss may have a multi‐faceted etiology, but the predominant mechanism is thought to be a phenomenon termed anabolic resistance. Anabolic resistance describes a refractoriness of muscle protein synthesis (MPS) to feeding‐induced hyperaminoacidemia in older versus younger persons. Older adults have a lower food intake and older women in particular may not be consuming adequate protein to stimulate MPS.ObjectiveTo determine whether the addition of leucine to a smaller dose (10g) of mixed milk protein can induce similar increases in acute and integrated myofibrillar MPS as an isoenergic, 25 g dose of whey protein isolate (WPI).MethodsHealthy, older women (n = 11/group) were recruited and randomized to one of 2 groups: 1) WPI: consumption of 25 g WPI (3 g leucine), 2/d or 2) P10: consumption of 10 g milk protein concentrate with 3 g leucine (Glanbia Nutritionals, PepForm®), 2/d. One leg was randomized to the exercised condition and maximal strength was determined (1‐RM). For determination of acute myofibrillar MPS, participants underwent primed constant infusion of 13C6‐phenylalanine and MPS was determined in the fasted, fed (rested) and fed + exercised (4 sets, 50–60% 1 RM, one leg) state. For determination of integrated myofibrillar MPS, participants consumed D2O (100 mL) and MPS was determined prior to (basal) and during supplementation in the rested and exercised leg. Participants were provided with all food to be consumed for 2 days prior to the acute trial (basal period) and throughout the 6 d supplementation period. The diet consisted of 1.0 g/kg/d protein. During the supplementation period the study beverages were incorporated into subjects' diets such that the participant continued to consume 1.0 g/kg/d protein.ResultsAcute myofibrillar MPS did not differ between groups in the fasted state. MPS increased in both the rested and exercised leg in response to P10 (fasted: 0.030 ± 0.003%/h, fed: 0.046 ± 0.003%/h, fed+exercise: 0.056 ± 0.002%/h; p &lt; 0.001) and WPI (fasted: 0.034 ± 0.001%/h, fed: 0.044 ± 0.002%/h, fed+exercise: 0.051 ± 0.002%/h; p &lt; 0.001), with no differences between groups. Acute MPS was greater in response to feeding in the exercised as compared with rested leg (p &lt; 0.001). There was no difference in basal rates of integrated myofibrillar MPS between groups (WPI: 1.52 ± 0.01%/d vs P10: 1.53 ± 0.03%/d). MPS increased with WPI during the supplementation period in both the rested (1.56 ± 0.02%/d, p = 0.02) and exercised (1.66 ± 0.02%/d, p &lt; 0.001) legs. MPS increased with P10 in the exercised leg (1.67 ± 0.02%/d, p &lt; 0.001) during the supplementation period with a trend for an increase in the rested leg (1.56 ± 0.02%/d, p = 0.1).ConclusionA lower (10 vs. 25 g) protein beverage with equal leucine content induced similar increases in acute and integrated myofibrillar MPS in healthy, older women. Lower protein nutritional supplements with added leucine may represent an advantageous approach in older adults to maintain skeletal muscle anabolic sensitivity and alleviate muscle loss.Support or Funding InformationPepsiCo Global R&amp;D

Greater Leucine Content Enhances the Acute and Integrated Muscle Protein Synthetic Responses Versus an Isonitrogenous, Isoenergetic Protein Beverage in Healthy Older Women

A decreased anabolic response to protein feeding is one of the mechanisms that underpins sarcopenic muscle loss with aging, with older adults requiring a higher protein dose than younger adults to increase muscle protein synthesis (MPS). Despite this knowledge, a number of commercially available protein beverages targeted to increase protein intake and support lean body mass in older adults contain ≤20 g of protein, and their ability to stimulate MPS in this population is unknown. Leucine has, however, been shown to enhance the MPS response to lower doses of protein and thus may represent an effective ‘anti‐sarcopenic’ ingredient.ObjectiveTo compare the acute and integrated myofibrillar MPS response to a typical commercial protein beverage to that of an isonitrogenous, isoenergetic protein beverage with added leucine in older women.MethodsHealthy, older women (n = 11/group) were recruited and randomized to one of 2 groups: 1) CON: 15 g mixed protein beverage (soy isolate, milk concentrate and caseinate), 2/d; 2) P15: 15 g milk protein concentrate with 4 g leucine (Glanbia Nutritionals, PepForm®), 2/d. Unilateral maximal strength was determined (1‐RM) and one leg was randomized to an exercise condition. For determination of acute MPS, participants underwent a primed constant infusion of 13C6‐phenylalanine and MPS was determined in the fasted, fed (rested) and fed + exercised (4 sets, 50–60% 1 RM, one leg) state. For determination of integrated MPS, participants consumed 100 mL of D2O and MPS was determined prior to (basal) and during 6 d supplementation in the rested and exercised leg. Participants were provided with all food to be consumed throughout the basal and supplementation period, which consisted of 1.0 g/kg/d protein. During the supplementation period the study beverages were incorporated into the diet such that the participant continued to consume 1.0 g/kg/d protein.ResultsAcute MPS was the same in the fasted state in both groups (CON: 0.034 ± 0.001%/h, P15: 0.034 ± 0.001%/h). Feeding increased MPS in the rested (CON: 0.038 ± 0.001%/h, P15: 0.053 ± 0.002%/h) and exercised (CON: 0.043 ± 0.001%/h, P15: 0.064 ± 0.002%/h) leg in both groups, but the increase was greater with P15 (p &lt; 0.001). Integrated MPS was the same in the basal state in both groups (CON: 1.52 ± 0.03%/d, P15: 1.48 ± 0.03%/d). MPS increased with P15 during the supplementation period in both legs (rested: 1.62 ± 0.03%/d, exercised: 1.73 ± 0.03%/d; p &lt; 0.001), but in the exercised leg only with CON (rested: 1.54 ± 0.02%/d, exercised: 1.62 ± 0.02%/d; p &lt; 0.001) and was greater with P15 than CON in both legs (p &lt; 0.001).ConclusionsA protein beverage fortified with 4 g of leucine induced greater increases in acute and integrated MPS than an isonitrogenous protein beverage containing protein equivalent to typical commercially available beverages. As opposed to consumption of P15, which increased MPS, chronic consumption of the CON protein beverage did not increase MPS and thus would not likely attenuate the loss of muscle mass in older adults.Support or Funding InformationPepsiCo Global R&amp;D

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.

Exercise Enhances The Overnight Muscle Protein Synthetic Response To Pre-sleep Protein Feeding In Older Males

PURPOSE: The age-related decline in skeletal muscle mass is, at least partly, attributed to anabolic resistance to food intake. To compensate for anabolic resistance, we recently introduced the ingestion of dietary protein prior to sleep as a nutritional strategy to increase overnight muscle protein synthesis rates. Here we aimed to assess whether resistance-type exercise performed in the evening can further augment the overnight muscle protein synthetic response to pre-sleep protein ingestion in older males. METHODS: In a parallel group design, twenty-three healthy older men (71±1 y) were randomly assigned to ingest 40 g casein protein before going to sleep with (PRO+EX: n=11) or without (PRO: n=12) performing resistance-type exercise earlier that evening. Overnight protein digestion and absorption kinetics, whole body protein metabolism and muscle myofibrillar protein synthesis rates were assessed using primed, continuous infusions of L-[ring-2H5]-phenylalanine and L-[ring-2H2]-tyrosine with the ingestion of intrinsically L-[1-13C]-phenylalanine labeled casein protein. RESULTS: Exogenous phenylalanine appearance rates expressed over time did not differ between treatments. A total of 53±2 vs 55±2% of the ingested protein-derived phenylalanine appeared in the circulation during overnight sleep in the PRO+EX and PRO treatment, respectively (P=0.49). Myofibrillar protein synthesis rates were 31% higher during overnight sleep when exercise was performed earlier that day (0.058±0.002 vs 0.044±0.003 %·h-1 in PRO+EX and PRO, respectively; P<0.01; L-[ring-2H5]-phenylalanine). In line, 27% more L-[1-13C]-phenylalanine was incorporated into myofibrillar protein in PRO+EX compared with PRO (0.042±0.002 vs 0.033±0.002 MPE, respectively; P<0.05; L-[1-13C]-phenylalanine). CONCLUSIONS: Resistance-type exercise augments the overnight muscle protein synthetic response to pre-sleep protein ingestion and allows more of the ingested protein to be directed towards de novo muscle protein synthesis during overnight sleep in older males. Funding: Top Institute Food and Nutrition (TIFN)

Fascicle length does increase in response to longitudinal resistance training and in a contraction-mode specific manner.

Fascicle length does increase in response to longitudinal resistance training and in a contraction-mode specific manner.

Preserved skeletal muscle protein anabolic response to acute exercise and protein intake in well-treated rheumatoid arthritis patients.

IntroductionRheumatoid arthritis (RA) is often associated with diminished muscle mass, reflecting an imbalance between protein synthesis and protein breakdown. To investigate the anabolic potential of both exercise and nutritional protein intake we investigated the muscle protein synthesis rate and anabolic signaling response in patients with RA compared to healthy controls.MethodsThirteen RA patients (age range 34–84 years; diagnosed for 1–32 years, median 8 years) were individually matched with 13 healthy controls for gender, age, BMI and activity level (CON). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay (ELISA) in resting blood samples obtained on two separate days. Skeletal muscle myofibrillar and connective tissue protein fractional synthesis rate (FSR) was measured by incorporation of the amino acid 13C6-phenylalanine tracer in the overnight fasted state for 3 hours (BASAL) and 3 hours after intake of whey protein (0.5 g/kg lean body mass) alone (PROT, 3 hrs) and in combination with knee-extensor exercise (EX) with one leg (8 × 10 reps at 70 % of 1RM; PROT + EX, 3 hrs). Expression of genes related to inflammatory signaling, myogenesis and muscle growth/atrophy were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).ResultsCRP was significantly higher in the RA patients (2.25 (0.50) mg/l) than in controls (1.07 (0.25) mg/l; p = 0.038) and so was TNF-α (RA 1.18 (0.30) pg/ml vs. CON 0.64 (0.07) pg/ml; p = 0.008). Muscle myofibrillar protein synthesis in both RA patients and CON increased in response to PROT and PROT + EX, and even more with PROT + EX (p < 0.001), with no difference between groups (p > 0.05). The gene expression response was largely similar in RA vs. CON, however, expression of the genes coding for TNF-α, myogenin and HGF1 were more responsive to exercise in RA patients than in CON.ConclusionsThe study demonstrates that muscle protein synthesis rate and muscle gene expression can be stimulated by protein intake alone and in combination with physical exercise in patients with well-treated RA to a similar extent as in healthy individuals. This indicates that moderately inflamed RA patients have maintained their muscle anabolic responsiveness to physical activity and protein intake.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0758-3) contains supplementary material, which is available to authorized users.

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.

Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression.

Key points Statins cause muscle‐specific side effects, most commonly muscle aches/weakness (myalgia), particularly in older people. Furthermore, evidence has linked statin use to increased risk of type 2 diabetes. However, the mechanisms involved are unknown.This is the first study to measure muscle protein turnover rates and insulin sensitivity in statin myalgic volunteers and age‐matched, non‐statin users under controlled fasting and fed conditions using gold standard methods.We demonstrate in older people that chronic statin myalgia is not associated with deficits in muscle strength and lean mass or the dysregulation of muscle protein turnover compared to non‐statin users. Furthermore, there were no between‐group differences in blood or muscle inflammatory markers.Statin users did, however, show blunting of muscle power output at the onset of dynamic exercise, increased abdominal adiposity, whole body and leg insulin resistance, and clear differential expression of muscle genes linked to mitochondrial dysfunction and apoptosis, which warrant further investigation. Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity. This is particularly relevant to older people who are less active, sarcopaenic and at increased risk of statin myalgia. We hypothesised that statin myalgia would be allied to impaired strength and work capacity in older people, and determined whether differences aligned with divergences in lean mass, protein turnover, insulin sensitivity and the molecular regulation of these processes. Knee extensor strength and work output during 30 maximal isokinetic contractions were assessed in healthy male volunteers, nine with no statin use (control 70.4 ± 0.7 years) and nine with statin myalgia (71.5 ± 0.9 years). Whole body and leg glucose disposal, muscle myofibrillar protein synthesis (MPS) and leg protein breakdown (LPB) were measured during fasting (≈5 mU l−1 insulin) and fed (≈40 mU l−1 insulin + hyperaminoacidaemia) euglyceamic clamps. Muscle biopsies were taken before and after each clamp. Lean mass, MPS, LPB and strength were not different but work output during the initial three isokinetic contractions was 19% lower (P < 0.05) in statin myalgic subjects due to a delay in time to reach peak power output. Statin myalgic subjects had reduced whole body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR. Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance, and evidence of mitochondrial dysfunction and apoptosis.

Role of Exercise and Nutrition in the Prevention of Sarcopenia

The age-associated loss of skeletal muscle mass and strength (sarcopenia) has been shown to increase the risk of injury due to falls and incidence of metabolic complications including insulin resistance and diabetes, which subsequently becomes a significant factor to disability among the elderly population. Nutrient intake is the most important anabolic stimulus for skeletal muscle. Specifically, the amino acid leucine and meal-induced insulin both independently stimulate muscle protein synthesis. However, age-specific changes in muscle anabolic responses to leucine become apparent when sub-maximal amounts of amino acids are administered in older subjects. Furthermore, insulin resistance of muscle protein metabolism with aging has been demonstrated in healthy non-diabetic older subjects. Resistance exercise is another anabolic stimulus which increases myofibrillar muscle protein synthesis in both young and older individuals. The increased muscle anabolism is apparent within 2-3 h after a single bout of heavy resistance exercise and remains elevated up to 2 d following the exercise. The mTOR signaling pathway in skeletal muscle is associated with an increased rate of muscle protein synthesis during the early recovery phase following a bout of resistance exercise. Finally, recent evidence on the cumulative effect of resistance exercise in combination with nutritional supplement on muscle protein metabolism will be discussed to propose a possible preventative measure against sarcopenia.

Leucine-Enriched Amino Acid Ingestion after Resistance Exercise Prolongs Myofibrillar Protein Synthesis and Amino Acid Transporter Expression in Older Men

Background:Postexercise protein or amino acid ingestion restores muscle protein synthesis in older adults and represents an important therapeutic strategy for aging muscle. However, the precise nutritional factors involved are unknown. Objective:The purpose of this study was to determine the role of increased postexercise Leu ingestion on skeletal muscle myofibrillar protein synthesis (MyoPS), mammalian/mechanistic target of rapamycin complex 1 signaling, and amino acid transporter (AAT) mRNA expression in older men over a 24-h post–resistance exercise (RE) time course. Methods:During a stable isotope infusion trial (L-[ring-13C6]Phe; L-[1-13C]Leu), older men performed RE and, at 1 h after exercise, ingested 10 g of essential amino acids (EAAs) containing either a Leu content similar to quality protein (control, 1.85 g of Leu, n = 7) or enriched Leu (LEU; 3.5 g of Leu, n = 8). Muscle biopsies (vastus lateralis) were obtained at rest and 2, 5, and 24 h after exercise. Results:p70 S6 kinase 1 phosphorylation was increased in each group at 2 h (P < 0.05), whereas 4E binding protein 1 phosphorylation increased only in the LEU group (P < 0.05). MyoPS was similarly increased (∼90%) above basal in each group at 5 h (P < 0.05) and remained elevated (∼90%) at 24 h only in the LEU group (P < 0.05). The mRNA expression of select AATs was increased at 2 and 5 h in each group (P < 0.05), but AAT expression was increased at 24 h only in the LEU group (P < 0.05). Conclusions:Leu-enriched EAA ingestion after RE may prolong the anabolic response and sensitivity of skeletal muscle to amino acids in older adults. These data emphasize the potential importance of adequate postexercise Leu ingestion to enhance the response of aging muscle to preventive or therapeutic exercise-based rehabilitation programs. This trial was registered at clinicaltrials.gov as NCT00891696.