Stimulation Of Myofibrillar Protein Synthesis Research Articles

Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice.

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D2O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-13C6 glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-13C6 glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism.

Evaluating the Effects of Increased Protein Intake on Muscle Strength, Hypertrophy and Power Adaptations with Concurrent Training: A Narrative Review.

Concurrent training incorporates dual exercise modalities, typically resistance and aerobic-based exercise, either in a single session or as part of a periodized training program, that can promote muscle strength, mass, power/force and aerobic capacity adaptations for the purposes of sports performance or general health/wellbeing. Despite multiple health and exercise performance-related benefits, diminished muscle hypertrophy, strength and power have been reported with concurrent training compared to resistance training in isolation. Dietary protein is well-established to facilitate skeletal muscle growth, repair and regeneration during recovery from exercise. The degree to which increased protein intake can amplify adaptation responses with resistance exercise, and to a lesser extent aerobic exercise, has been highly studied. In contrast, much less focus has been directed toward the capacity for protein to enhance anabolic and metabolic responses with divergent contractile stimuli inherent to concurrent training and potentially negate interference in muscle strength, power and hypertrophy. This review consolidates available literature investigating increased protein intake on rates of muscle protein synthesis, hypertrophy, strength and force/power adaptations following acute and chronic concurrent training. Acute concurrent exercise studies provide evidence for the significant stimulation of myofibrillar protein synthesis with protein compared to placebo ingestion. High protein intake can also augment increases in lean mass with chronic concurrent training, although these increases do not appear to translate into further improvements in strength adaptations. Similarly, the available evidence indicates protein intake twice the recommended intake and beyond does not rescue decrements in selective aspects of muscle force and power production with concurrent training.

Myofibrillar protein synthesis and muscle hypertrophy individualized responses to systematically changing resistance training variables in trained young men.

The manipulation of resistance training (RT) variables is used among athletes, recreational exercisers, and compromised populations (e.g., elderly) attempting to potentiate muscle hypertrophy. However, it is unknown whether an individual's inherent predisposition dictates the RT-induced muscle hypertrophic response. Resistance-trained young [26 (3) y] men (n = 20) performed 8 wk unilateral RT (2 times/wk), with 1 leg randomly assigned to a standard progressive RT [control (CON)] and the contralateral leg to a variable RT (VAR; modulating exercise load, volume, contraction type, and interset rest interval). The VAR leg completed all 4 RT variations every 2 wk. Bilateral vastus lateralis cross-sectional area (CSA) was measured, pre- and post-RT and acute integrated myofibrillar protein synthesis (MyoPS) rates were assessed at rest and over 48 h following the final RT session. Muscle CSA increase was similar between CON and VAR (P > 0.05), despite higher total training volume (TTV) in VAR (P < 0.05). The 0-48-h integrated MyoPS increase postexercise was slightly greater for VAR than CON (P < 0.05). All participants were considered "responders" to RT, although none benefited to a greater extent from a specific protocol. Between-subjects variability (MyoPS, 3.30%; CSA, 37.8%) was 40-fold greater than the intrasubject (between legs) variability (MyoPS, 0.08%; CSA, 0.9%). The higher TTV and greater MyoPS response in VAR did not translate to a greater muscle hypertrophic response. Manipulating common RT variables elicited similar muscle hypertrophy than a standard progressive RT program in trained young men. Intrinsic individual factors are key determinants of the MyoPS and change in muscle CSA compared with extrinsic manipulation of common RT variables.NEW & NOTEWORTHY Systematically manipulating resistance training (RT) variables during RT augments the stimulation of myofibrillar protein synthesis (MyoPS) and training volume but fails to potentiate muscle hypertrophy compared with a standard progressive RT. Any modest further MyoPS increase and higher training volumes do not reflect in a greater hypertrophic response. Between-subject variability was 40-fold greater than the variability promoted by extrinsic manipulation of RT variables, indicating that individual intrinsic factors are stronger determinants of the hypertrophic response.

Consumption of whole eggs promotes greater stimulation of postexercise muscle protein synthesis than consumption of isonitrogenous amounts of egg whites in young men

Background: Protein in the diet is commonly ingested from whole foods that contain various macro- and micronutrients. However, the effect of consuming protein within its natural whole-food matrix on postprandial protein metabolism remains understudied in humans.Objective: We aimed to compare the whole-body and muscle protein metabolic responses after the consumption of whole eggs with egg whites during exercise recovery in young men.Design: In crossover trials, 10 resistance-trained men [aged 21 ± 1 y; 88 ± 3 kg; body fat: 16% ± 1% (means ± SEMs)] received primed continuous l-[ring-2H5]phenylalanine and l-[1-13C]leucine infusions and performed a single bout of resistance exercise. After exercise, participants consumed intrinsically l-[5,5,5-2H3]leucine-labeled whole eggs (18 g protein, 17 g fat) or egg whites (18 g protein, 0 g fat). Repeated blood and muscle biopsy samples were collected to assess whole-body leucine kinetics, intramuscular signaling, and myofibrillar protein synthesis.Results: Plasma appearance rates of protein-derived leucine were more rapid after the consumption of egg whites than after whole eggs (P = 0.01). Total plasma availability of leucine over the 300-min postprandial period was similar (P= 0.75) between the ingestion of whole eggs (68% ± 1%) and egg whites (66% ± 2%), with no difference in whole-body net leucine balance (P = 0.27). Both whole-egg and egg white conditions increased the phosphorylation of mammalian target of rapamycin complex 1, ribosomal protein S6 kinase 1, and eukaryotic translation initiation factor 4E-binding protein 1 during postexercise recovery (all P < 0.05). However, whole-egg ingestion increased the postexercise myofibrillar protein synthetic response to a greater extent than did the ingestion of egg whites (P= 0.04).Conclusions: We show that the ingestion of whole eggs immediately after resistance exercise resulted in greater stimulation of myofibrillar protein synthesis than did the ingestion of egg whites, despite being matched for protein content in young men. Our data indicate that the ingestion of nutrient- and protein-dense foods differentially stimulates muscle anabolism compared with protein-dense foods. This trial was registered at clinicaltrials.gov as NCT03117127.

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.

Differences in postprandial protein handling after beef compared with milk ingestion during postexercise recovery: a randomized controlled trial

Protein consumed after resistance exercise increases postexercise muscle protein synthesis rates. To date, dairy protein has been studied extensively, with little known about the capacity of other protein-dense foods to augment postexercise muscle protein synthesis rates. We aimed to compare protein digestion and absorption kinetics, postprandial amino acid availability, anabolic signaling, and the subsequent myofibrillar protein synthetic response after the ingestion of milk compared with beef during recovery from resistance-type exercise. In crossover trials, 12 healthy young men performed a single bout of resistance exercise. Immediately after cessation of exercise, participants ingested 30 g protein by consuming isonitrogenous amounts of intrinsically l-[1-(13)C]phenylalanine-labeled beef or milk. Blood and muscle biopsy samples were collected at rest and after exercise during primed continuous infusions of l-[ring-(2)H5]phenylalanine and l-[ring-3,5-(2)H2]tyrosine to assess protein digestion and absorption kinetics, plasma amino acid availability, anabolic signaling, and subsequent myofibrillar protein synthesis rates in vivo in young men. Beef protein-derived phenylalanine appeared more rapidly in circulation compared with milk ingestion (P < 0.001). The availability of phenylalanine during the 5-h postexercise period tended to be higher after beef (64% ± 3%) ingestion than after milk ingestion (57% ± 3%; P = 0.08). Both beef and milk ingestion were followed by an increase in the phosphorylation of mammalian target of rapamycin complex 1 and 70-kDa S6 protein kinase 1 during postexercise recovery. Milk ingestion increased myofibrillar protein synthesis rates to a greater extent than did beef ingestion during the 0- to 2-h postexercise phase (P = 0.013). However, the increase in myofibrillar protein synthesis rates did not differ between milk and beef ingestion during the entire 0- to 5-h postexercise phase (P = 0.114). Both milk and beef ingestion augment the postexercise myofibrillar protein synthetic response in young men, with a stronger stimulation of myofibrillar protein synthesis during the early postprandial stage after milk ingestion. This trial was registered at www.clinicaltrials.gov as NCT01578590.

Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men.

Adequate protein ingestion-mediated stimulation of myofibrillar protein synthesis (MPS) is required to maintain skeletal muscle mass. It is currently unknown what per meal protein intake is required to maximally stimulate the response in older men and whether it differs from that of younger men. We retrospectively analyzed data from our laboratories that measured MPS in healthy older (~71 years) and younger (~22 years) men by primed constant infusion of l-ring-[(13)C6]phenylalanine after ingestion of varying amounts (0-40 g) of high-quality dietary protein as a single bolus and normalized to body mass and, where available, lean body mass (LBM). There was no difference (p = .53) in basal MPS rates between older (0.027±0.04%/h; means ± 95% CI) and young (0.028 ± 0.03%/h) men. Biphase linear regression and breakpoint analysis revealed the slope of first line segment was lower (p < .05) in older men and that MPS reached a plateau after ingestion of 0.40 ± 0.19 and 0.24 ± 0.06 g/kg body mass (p = .055) and 0.60 ± 0.29 and 0.25 ± 0.13 g/kg lean body mass (p < .01) in older and younger men, respectively. This is the first report of the relative (to body weight) protein ingested dose response of MPS in younger and older men. Our data suggest that healthy older men are less sensitive to low protein intakes and require a greater relative protein intake, in a single meal, than young men to maximally stimulate postprandial rates of MPS. These results should be considered when developing nutritional solutions to maximize MPS for the maintenance or enhancement of muscle mass with advancing age.

Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men

We aimed to determine the effect of consuming pure isolated micellar casein or pure whey protein isolate on rates of myofibrillar protein synthesis (MPS) at rest and after resistance exercise in elderly men. Healthy elderly men (72 (sem 1) years; BMI 26·4 (sem 0·7) kg/m²) were divided into two groups (n 7 each) who received a primed, constant infusion of l-[ring-¹³C₆]phenylalanine to measure MPS at rest and during 4 h of exercise recovery. Participants performed unilateral leg resistance exercise followed by the consumption of isonitrogenous quantities (20 g) of casein or whey. Blood essential amino acids and leucine concentration peaked 60 min post-drink and were greater in amplitude after whey protein ingestion (both, P < 0·05). MPS in the rested leg was 65 % higher (P = 0·002) after ingestion of whey (0·040 (sem 0·003) %/h) when compared with micellar casein (0·024 (sem 0·002) %/h). Similarly, resistance exercise-stimulated rates of MPS were greater (P < 0·001) after whey ingestion (0·059 (sem 0·005) %/h) v. micellar casein (0·035 (sem 0·002) %/h). We conclude that ingestion of isolated whey protein supports greater rates of MPS than micellar casein both at rest and after resistance exercise in healthy elderly men. This result is probably related to a greater hyperaminoacidaemia or leucinaemia with whey ingestion.

No role for early IGF-1 signalling in stimulating acute ‘muscle building’ responses

No role for early IGF-1 signalling in stimulating acute ‘muscle building’ responses

Exercise intensity matters for both young and old muscles

Exercise intensity matters for both young and old muscles

The battle to keep or lose skeletal muscle with ageing

Ageing is associated with both a loss in muscle mass and a loss in skeletal muscle metabolic quality. These changes lead to sarcopenia and subsequent reduced daily function, and increase the risk for fall and fractures. Also, the metabolic deficits result in an increased risk for insulin resistance, obesity and type 2 diabetes. A major part – but not all – of these age-associated changes are related to a decreased level of physical activity, and thus this age-associated loss can be partly counteracted by increased physical activity. Resistance training in particular has been documented to have beneficial effects upon muscle mass and strength also in very old untrained people (Fiatarone et al. 1990; Welle et al. 1993; Sheffield-Moore et al. 2005). How much and how intense should elderly people perform strength training in order to counteract their age-associated loss in skeletal muscle mass remains a challenge, and only few studies have addressed this issue. In this issue of The Journal of Physiology, the Rennie group (Kumar et al. 2009) document that older compared to young individuals demonstrate a blunted rise in myofibrillar protein synthesis after exercise, and that this was associated with a lower response in the phosphorylation of two of the post-translational modification factors, p70 ribosomal S6 kinase (p70s6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). The correlation between protein synthesis and regulatory factors adds to our present knowledge, but clearly still represents associations, and the statement that p70s6K predicts rate of myofibrillar synthesis rate in young but not in old is somewhat optimistic. It does, however, support the view that elderly demonstrate a certain ‘anabolic resistance’, a finding that earlier has been supported by the same research group in relation to nutritional intake, where elderly demonstrated less stimulation of myofibrillar protein synthesis than younger counterparts when challenged with increasing circulating levels of amino acids (Cuthbertson et al. 2005).

High-protein meals do not enhance myofibrillar synthesis after resistance exercise in 62- to 75-yr-old men and women.

This study tested the hypothesis that increasing the protein content of isocaloric meals increases the rate of myofibrillar synthesis in muscle of healthy subjects over 60 yr old and enhances the stimulation of myofibrillar synthesis induced by resistance exercise. Myofibrillar synthesis of sedentary and exercised quadriceps muscle was determined by incorporation of L-[1-13C]leucine. During the tracer infusion, subjects consumed meals with a low (7% of energy, n = 6)-, normal (14%, n = 6)-, or high (28%, n = 6)-protein content. In sedentary muscle, the mean (+/- SE) myofibrillar synthesis was 1.56 +/- 0.13%/day in the low-protein group, 1.73 +/- 0.11 %/day in the normal-protein group, and 1.76 +/- 0.10%/day in the high-protein group (P = 0.42). Myofibrillar synthesis was faster in exercised muscle (mean 27%, P < 10(-6) in all groups (2.10 +/- 0.14%/day in low protein; 2.18 +/- 0.10%/day in normal protein; 2.11 +/- 0.09%/day in high protein; P = 0.84). The stimulation of myofibrillar synthesis by exercise was not significantly different among low-protein [0.54 +/- 0.12%/day (37 +/- 9%)], normal-protein [0.46 +/- 0.08%/day (28 +/- 5%)], and high-protein groups [0.34 +/- 0.04%/day (20 +/- 3%); P = 0.31]. We conclude that high-protein meals do not enhance the stimulation of myofibrillar protein synthesis induced by resistance exercise.

Stimulation of myofibrillar protein synthesis in hindlimb suspended rats by resistance exercise and growth hormone

The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1m grid (85 °), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30′ prior to exercise, and Ks was determined with a constant infusion of 3H-Leucine at 15′, 60′, 180′, and 360′ following exercise. Three days of HLS depressed Ks 6̃5% and 30–40% in the soleus and gastrocnemius muscles, respectively (p<-.05). Exercise increased soleus Ks in saline-treated rats 149% 60′ following exercise (p<-.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH+exercise increased soleus Ks 84%, 108%, and 72% at 15′, 60′ and 360′ following exercise (p<-.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360′ post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60′ post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

Porcine Skeletal Muscle Myofibrillar Protein Synthesis is Stimulated by Ractopamine ,

Thirty-two 64-kg individually penned barrows were fed protein at 130 or 170 g/kg diet and ractopamine at 0 or 20 mg/kg in a randomized complete block design for 28 d. Fractional synthesis rates of myofibrillar, sarcoplasmic and connective tissue proteins in longissimus dorsi, biceps femoris and gastrocnemius muscles were examined by primed-continuous infusion of L-[ring-2,6-3H(N)]phenylalanine over a 4-h period. Fractional synthesis, accretion and breakdown rates of protein in the muscles were not affected by dietary ractopamine, regardless of whether estimated on the basis of plasma or tissue homogenate specific activity. Absolute rates of protein synthesis (P < 0.05) and breakdown (P < 0.1) in biceps femoris muscle were both elevated by ractopamine feeding at 170 g protein/kg diet. Also in the diet containing 170 g protein/kg, ractopamine increased (P < 0.05) protein contents of longissimus dorsi and biceps femoris muscles. Dietary ractopamine increased (P < 0.05) fractional rates of synthesis of myofibrillar but not sarcoplasmic proteins in longissimus dorsi and biceps femoris muscles of pigs fed the 170 g protein/kg diet. This result demonstrates that ractopamine treatment results in a stimulation of myofibrillar protein synthesis.