Muscle Protein Synthetic Response Research Articles

Leucine Supplementation Increases Muscle Strength and Volume, Reduces Inflammation, and Affects Wellbeing in Adults and Adolescents with Cerebral Palsy

BackgroundSpastic cerebral palsy (CP) is characterized by muscle weakness owing, in part, to a blunted muscle protein synthetic response. This might be normalized by long-term leucine supplementation. ObjectivesThe study assessed the effects of 10 wk leucine supplementation in adolescents and adults with CP. MethodsThe study was a single-center randomized controlled trial. Twenty-four participants were randomly assigned to a control group (n = 12) or a leucine group (n = 12). l-Leucine (192 mg/kg body mass) was dissolved in water and administered daily for 10 wk. The primary outcome measures of elbow flexor muscle strength and muscle volume (measured by 3D ultrasound technique) and inflammation [C-reactive protein (CRP) concentration] were assessed before and after the 10 wk, alongside the secondary outcomes of body composition (measured by CP-specific skinfold assessment), metabolic rate (measured by indirect calorimetry), and wellbeing (measured by a self-reported daily questionnaire). Data were compared via a series of 2-factor mixed ANOVAs. ResultsTwenty-one participants completed the intervention (control group: n = 11, mean ± SD age: 18.3 ± 2.8 y, body mass: 48.8 ± 11.9 kg, 45% male; leucine group: n = 10, age: 18.6 ± 1.7 y, body mass: 58.3 ± 20.2 kg, 70% male). After 10 wk, there was a 25.4% increase in strength (P = 0.019) and a 3.6% increase in muscle volume (P = 0.001) in the leucine group, with no changes in the control group. This was accompanied by a 59.1% reduction in CRP (P = 0.045) and improved perceptions of wellbeing (P = 0.006) in the leucine group. No changes in metabolism or body composition were observed in either group (P > 0.05). ConclusionsImprovements in muscle strength and volume with leucine supplementation might provide important functional changes for adults and adolescents with CP and could be partly explained by reduced inflammation. The improved wellbeing highlights its capacity to improve the quality of daily living. This trial was registered at http://www.clinicaltrials.gov as NCT03668548.

Ingestion of a bolus of free amino acids is followed by more rapid amino acid absorption and greater postprandial plasma amino acid availability when compared to the ingestion of an equivalent amount of intact protein

Rationale: The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates. This study compares protein digestion and amino acid absorption kinetics and the subsequent muscle protein synthetic response following ingestion of intact protein versus the equivalent amount of free crystalline amino acids.

Dietary protein interventions to improve nutritional status in end-stage renal disease patients undergoing hemodialysis.

Poor nutritional status is prevalent among end-stage renal disease patients undergoing hemodialysis. Chronic hemodialysis patients show an accelerated decline in skeletal muscle mass and strength, which is associated with higher mortality rates and a reduced quality of life. The current review aims to summarize recent advances regarding underlying causes of muscle loss and interventions that support muscle mass maintenance in patients with chronic hemodialysis. Muscle maintenance in chronic hemodialysis patients is compromised by low dietary protein intake levels, anabolic resistance of skeletal muscle tissue, sedentary behavior, and amino acid removal during hemodialysis. Studies assessing the effect of increased protein intake on nutritional status generally show beneficial results, especially in hypoalbuminemic chronic hemodialysis patients. The muscle protein synthetic response following protein ingestion in chronic hemodialysis patients may be enhanced through incorporation of structured physical activity and/or concurrent ketoacid ingestion. A coordinated program that combines nutritional and physical activity interventions is likely required to attenuate the decline in muscle mass and strength of chronic hemodialysis patients. Nephrologists, dieticians, and exercise specialists should collaborate closely to establish guidelines regarding the appropriate quantity and timing of protein ingestion. In addition, they should provide tailored nutritional and physical activity interventions for chronic hemodialysis patients (see video, Supplemental Digital Content 1, Video abstract, http://links.lww.com/COCN/A14).

Mycoprotein ingestion stimulates protein synthesis rates to a greater extent than milk protein in rested and exercised skeletal muscle of healthy young men: a randomized controlled trial

Mycoprotein is a fungal-derived sustainable protein-rich food source, and its ingestion results in systemic amino acid and leucine concentrations similar to that following milk protein ingestion. We assessed the mixed skeletal muscle protein synthetic response to the ingestion of a single bolus of mycoprotein compared with a leucine-matched bolus of milk protein, in rested and exercised muscle of resistance-trained young men. Twenty resistance-trained healthy young males (age: 22±1 y, body mass: 82±2 kg, BMI: 25±1 kg·m-2) took part in a randomized, double-blind, parallel-group study. Participants received primed, continuous infusions of L-[ring-2H5]phenylalanine and ingested either 31 g (26.2 g protein: 2.5 g leucine) milk protein (MILK) or 70 g (31.5 g protein: 2.5 g leucine) mycoprotein (MYCO) following a bout of unilateral resistance-type exercise (contralateral leg acting as resting control). Blood and m. vastus lateralis muscle samples were collected before exercise and protein ingestion, and following a 4-h postprandial period to assess mixed muscle fractional protein synthetic rates (FSRs) and myocellular signaling in response to the protein beverages in resting and exercised muscle. Mixed muscle FSRs increased following MILK ingestion (from 0.036±0.008 to 0.052±0.006%·h-1 in rested, and 0.035±0.008 to 0.056±0.005%·h-1 in exercised muscle; P<0.01) but to a greater extent following MYCO ingestion (from 0.025±0.006 to 0.057±0.004%·h-1 in rested, and 0.024±0.007 to 0.072±0.005%·h-1 in exercised muscle; P<0.0001) (treatment×time interaction effect; P<0.05). Postprandial FSRs trended to be greater in MYCO compared with MILK (0.065±0.004 compared with 0.054±0.004%·h-1, respectively; P=0.093) and the postprandial rise in FSRs was greater in MYCO compared with MILK (Delta 0.040±0.006 compared with Delta 0.018±0.005%·h-1, respectively; P<0.01). The ingestion of a single bolus of mycoprotein stimulates resting and postexercise muscle protein synthesis rates, and to a greater extent than a leucine-matched bolus of milk protein, in resistance-trained young men. This trial was registered at clinicaltrials.gov as 660065600.

Energy Deficit Attenuates Muscle Protein Synthetic Responses To Essential Amino Acids

BACKGROUND: Peripheral essential amino acid (EAA) concentrations regulate muscle protein synthesis (MPS). During energy balance, consuming ~9 g EAA doubles postprandial peripheral EAA concentrations and increases resting MPS by nearly 50%. During energy deficit, EAA requirements may be elevated due to a greater carbon skeleton requirement for energy metabolism. We examined if similar or greater increases in peripheral EAA concentrations during energy deficit stimulate the same magnitude increase in MPS as in energy balance. PURPOSE: Determine the effects of peripheral increases in EAA concentrations and the stimulation of MPS during energy balance and deficit. METHODS: Data were derived from two independent controlled studies assessing the effects of consuming high and low doses of EAA on peripheral EAA concentrations and MPS (2H5-phenylanine, direct incorporation method) during energy balance (BAL HIGH/LOW) and energy deficit (DEF HIGH/LOW). In BAL, measures were determined in 8 healthy adults (mean ± SD; 21.4 ± 2 y, 24.6 ± 3.2 kg/m2 ), ingesting in random order, either 4.3 ± 0.0 g or 8.6 ± 0.0 g EAA, separated by 7 d. In DEF, measures followed 5 days of controlled energy deficit (30 ± 4 %) in 19 healthy adults (22.9 ± 5 y, 25.4 ± 2.7 kg/m2), ingesting either 7.8 ± 0.9 g or 23.5 ± 2.6 g EAA, in random order, separated by 14 d. RESULTS: Peak EAA concentrations were 36% higher in DEF HIGH compared to BAL HIGH (2219 ± 470 vs. 1634 ± 320 μmol/L; p<0.05), but not for the low doses. Peak EAA concentrations were higher (p<0.05) in HIGH doses for both energy states compared to LOW doses. Independent of EAA dose, postprandial MPS for BAL (0.78 ± 0.36 %/h) and DEF (0.58 ± 0.15 %/h) were 81% and 26% greater than postabsorptive MPS for BAL (0.43 ± 0.18 %/h) and DEF (0.46 ± 0.24 %/h), respectively (energy-by-fed state, p<0.05). Postprandial MPS was 25% lower in DEF than BAL (energy-by-state, p<0.05). CONCLUSION: Ingesting roughly triple the dose of EAA in DEF than BAL (23.5 g vs. 8.6 g) resulted in marked differences in peripheral concentrations; yet the anabolic stimulus was similar. The reduction in postprandial MPS during DEF, despite ingesting 2-3 times the amount of EAA compared to BAL, suggests that muscle is not the primary target for the greater rise in peripheral EAA. Supported by USAMRDC; authors’ views not official U.S. Army or DoD policy.

The Impact of Protein Supplementation on Exercise-Induced Muscle Damage, Soreness and Fatigue Following Prolonged Walking Exercise in Vital Older Adults: A Randomized Double-Blind Placebo-Controlled Trial.

Background: It is unknown whether protein supplementation can enhance recovery of exercise-induced muscle damage in older adults who have a disturbed muscle protein synthetic response. We assessed whether protein supplementation could attenuate exercise-induced muscle damage and soreness after prolonged moderate-intensity walking exercise in older adults. Methods: In a double-blind, placebo-controlled intervention study, 104 subjects (81% male, ≥65 years) used either a protein (n = 50) or placebo supplement (n = 54) during breakfast and directly after exercise. Within a walking event, study subjects walked 30/40/50 km per day on three consecutive days. Muscle soreness and fatigue were determined with a numeric rating scale, and creatine kinase (CK) concentrations and serum inflammation markers were obtained. Results: Habitual protein intake was comparable between the protein (0.92 ± 0.27 g/kg/d) and placebo group (0.97 ± 0.23 g/kg/d, p = 0.31). At baseline, comparable CK concentrations were found between the protein and the placebo group (110 (IQR: 84–160 U/L) and 115 (IQR: 91–186 U/L), respectively, p = 0.84). Prolonged walking (protein: 32 ± 9 km/d, placebo: 33 ± 6 km/d) resulted in a cumulative increase of CK in both the protein (∆283 (IQR: 182–662 U/L)) and placebo group (∆456 (IQR: 209–885 U/L)) after three days. CK elevations were not significantly different between groups (p = 0.43). Similarly, no differences in inflammation markers, muscle soreness and fatigue were found between groups. Conclusions: Protein supplementation does not attenuate exercise-induced muscle damage, muscle soreness or fatigue in older adults performing prolonged moderate-intensity walking exercise.

The Muscle Protein Synthetic Response Following Ingestion of Corn Protein, Milk Protein and Their Protein Blend in Young Males

Abstract Objectives The muscle protein synthetic response to the ingestion of animal based proteins has been reported to be superior to the ingestion of plant based proteins. The lesser anabolic properties of plant based compared with animal based proteins has been attributed to differences in essential amino acid (EAA) contents and amino acid composition. This study compares post-prandial muscle protein synthesis rates following the ingestion of 30 g milk protein with the ingestion of 30 g corn protein or a blend of 30 g corn and milk protein in vivo, in young males. Methods In a randomized, double blind, parallel-group design, 36 healthy young males (26 ± 4 y) received a primed continuous infusion of L-[ring-13C6]-phenylalanine and ingested 30 g milk protein (MILK), 30 g corn protein (CORN), or a blend of 15 g corn protein plus 15 g milk protein (CORN + MILK) (n = 12 per group). Blood and muscle biopsies were collected for 5 h following protein ingestion to assess post-prandial plasma amino acid profiles and myofibrillar protein synthesis rates. Data were analyzed with 2-way repeated measures ANOVA and independent samples t-test. Data are expressed as mean ± SD. Results MILK increased plasma EAA concentrations more when compared to CORN (incremental area under curve (iAUC): 151 ± 31 vs 77 ± 19 mmol/L/300 min, respectively; P &amp;lt; 0.001). Both milk and corn protein ingestion increased myofibrillar protein synthesis rates (P &amp;lt; 0.001), with no differences between MILK and CORN (from 0.014 ± 0.014 to 0.053 ± 0.013 and from 0.017 ± 0.011 to 0.052 ± 0.013%/h, respectively; time*treatment P = 0.661). When MILK was compared to CORN + MILK, the iAUC for plasma EAA concentrations increased more in MILK when compared to CORN + MILK (151 ± 31 vs 126 ± 24 mmol/L/300 min, respectively; P = 0.036). Corn plus milk protein ingestion also increased myofibrillar protein synthesis rates (from 0.015 ± 0.015 to 0.052 ± 0.024%/h; P &amp;lt; 0.001), with no differences between MILK and CORN + MILK (time*treatment P = 0.823). Conclusions Ingestion of 30 g milk protein, 30 g corn protein, or a blend of 15 g corn plus 15 g milk protein increases muscle protein synthesis rates in vivo in young males. Post-prandial muscle protein synthesis rates following the ingestion of 30 g milk protein do not differ from rates observed after ingesting 30 g corn protein or a blend providing 15 g milk plus 15 g corn protein in vivo, in young males. Funding Sources TiFN.

Ingestion of Free Amino Acids as Opposed to Intact Protein Increases Amino Acid Absorption but Does Not Further Augment Postprandial Muscle Protein Synthesis Rates

Abstract Objectives The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and, as such, modulates postprandial muscle protein synthesis rates. This study compares protein digestion and amino acid absorption kinetics and the subsequent muscle protein synthetic response following ingestion of intact protein versus an equivalent amount of free, crystalline amino acids. Methods Twenty-four healthy, young subjects (age: 22 ± 3 y, BMI: 23 ± 2 kg·m−2, sex: 12 M/12F) ingested 30 g intrinsically L-[1–13C]-phenylalanine and L-[1–13C]-leucine labeled milk protein (PROT; n = 12) or an equivalent amount of free amino acids (AA; n = 12). In addition, subjects received primed continuous L-[ring-2H5]-phenylalanine, L-[ring-3,5–2H2]-tyrosine, and L-[1–13C]-leucine infusions. Blood samples and muscle biopsies were obtained frequently to assess protein digestion and amino acid absorption kinetics and subsequent muscle protein synthesis rates over a 6 h postprandial period. An unpaired t-test was used to compare overall exogenous phenylalanine release in plasma. For other parameters repeated measures ANOVA were applied to determine differences between groups over time (time as within, and group as between-subjects factor). Data are expressed as mean ± SD. Results Postprandial plasma amino acid concentrations and exogenous phenylalanine appearance rates increased after ingestion of PROT and AA (both, P &amp;lt; 0.001), with a greater increase following ingestion of AA when compared to PROT (time*group interaction P &amp;lt; 0.001). Exogenous phenylalanine release in plasma assessed over the 6 h postprandial period, was greater in AA (76 ± 9%) compared with PROT (59 ± 10%; P &amp;lt; 0.001). Ingestion of AA and PROT strongly increased muscle protein synthesis rates based upon L-[ring-2H5]-phenylalanine (time effect P &amp;lt; 0.001), with no differences between groups (from 0.037 ± 0.015 to 0.053 ± 0.014%·h−1 and from 0.039 ± 0.016 to 0.051 ± 0.010%·h−1, respectively; time*group interaction P = 0.629). Conclusions Ingestion of free amino acids as opposed to intact milk protein is followed by more rapid amino acid absorption and greater postprandial plasma amino acid availability, but this does not further augment postprandial muscle protein synthesis rates. Funding Sources This research did not receive external funding.

Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight, and obese men.

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m2] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m2) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher (P < 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 (P = 0.06) and ceramide C16:0 (P < 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.

Dietary Protein and Physical Activity Interventions to Support Muscle Maintenance in End-Stage Renal Disease Patients on Hemodialysis.

End-stage renal disease patients have insufficient renal clearance capacity left to adequately excrete metabolic waste products. Hemodialysis (HD) is often employed to partially replace renal clearance in these patients. However, skeletal muscle mass and strength start to decline at an accelerated rate after initiation of chronic HD therapy. An essential anabolic stimulus to allow muscle maintenance is dietary protein ingestion. Chronic HD patients generally fail to achieve recommended protein intake levels, in particular on dialysis days. Besides a low protein intake on dialysis days, the protein equivalent of a meal is extracted from the circulation during HD. Apart from protein ingestion, physical activity is essential to allow muscle maintenance. Unfortunately, most chronic HD patients have a sedentary lifestyle. Yet, physical activity and nutritional interventions to support muscle maintenance are generally not implemented in routine patient care. To support muscle maintenance in chronic HD patients, quantity and timing of protein intake should be optimized, in particular throughout dialysis days. Furthermore, implementing physical activity either during or between HD sessions may improve the muscle protein synthetic response to protein ingestion. A well-orchestrated combination of physical activity and nutritional interventions will be instrumental to preserve muscle mass in chronic HD patients.

Mycoprotein and Muscle Protein Synthetic Response

Mycoprotein and Muscle Protein Synthetic Response

The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle

Sarcopenia is defined as the combined loss of skeletal muscle strength, function, and/or mass with aging. This degenerative loss of muscle mass is associated with poor quality of life and early mortality humans. The loss of muscle mass occurs due to acute changes in daily muscle net protein balance (NPB). It is generally believed a poor NPB occurs due to reduced muscle protein synthetic responses to exercise, dietary amino acid availability, or an insensitivity of insulin to suppress breakdown. Hence, aging muscles appear to be resistant to the anabolic action of exercise and protein (amino acids or hormonal) when compared to their younger counterparts. The mechanisms that underpin anabolic resistance to anabolic stimuli (protein and resistance exercise) are multifactorial and may be partly driven by poor lifestyle choices (increased sedentary time and reduced dietary protein intake) as well as an inherent dysregulated mechanism in old muscles irrespective of the environmental stimuli. The insulin like growth factor 1 (IGF-1), Akt /Protein Kinase B and mechanistic target of rapamycin (mTOR) pathway is the primary driver between mechanical contraction and protein synthesis and may be a site of dysregulation between old and younger people. Therefore, our review aims to describe and summarize the differences seen in older muscle in this pathway in response to resistance exercise (RE) and describe approaches that researchers have sought out to maximize the response in muscle. Furthermore, this review will present the hypothesis that inositol hexakisphosphate kinase 1 (IP6K1) may be implicated in IGF-1 signaling and thus sarcopenia, based on recent evidence that IGF-1 and insulin share some intracellular bound signaling events and that IP6K1 has been implicated in skeletal muscle insulin resistance.

Basal and Postprandial Myofibrillar Protein Synthesis Rates Do Not Differ between Lean and Obese Middle-Aged Men

ABSTRACTBackgroundExcess lipid availability has been associated with the development of anabolic resistance. As such, obesity may be accompanied by impairments in muscle protein metabolism.ObjectiveWe hypothesized that basal and postprandial muscle protein synthesis rates are lower in obese than in lean men.MethodsTwelve obese men [mean ± SEM age: 48 ± 2 y; BMI (in kg/m2): 37.0 ± 1.5; body fat: 32 ± 2%] and 12 age-matched lean controls (age: 43 ± 3 y; BMI: 23.4 ± 0.4; body fat: 21 ± 1%) received primed continuous L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine infusions and ingested 25 g intrinsically L-[1-13C]-phenylalanine labeled whey protein. Repeated blood and muscle samples were obtained to assess protein digestion and amino acid absorption kinetics, and basal and postprandial myofibrillar protein synthesis rates.ResultsExogenous phenylalanine appearance rates increased after protein ingestion in both groups (P < 0.001), with a total of 53 ± 1% and 53 ± 2% of dietary protein–derived phenylalanine appearing in the circulation over the 5-h postprandial period in lean and obese men, respectively (P = 0.82). After protein ingestion, whole-body protein synthesis and oxidation rates increased to a greater extent in lean men than in the obese (P-interaction < 0.05), resulting in a higher whole-body protein net balance in the lean than in the obese (7.1 ± 0.2 and 4.6 ± 0.4 µmol phenylalanine · h−1 · kg−1, respectively; P-interaction < 0.001). Myofibrillar protein synthesis rates increased from 0.030 ± 0.002 and 0.028 ± 0.003%/h in the postabsorptive period to 0.034 ± 0.002 and 0.035 ± 0.003%.h−1 in the 5-h postprandial period (P = 0.03) in lean and obese men, respectively, with no differences between groups (P-interaction = 0.58).ConclusionsBasal, postabsorptive myofibrillar protein synthesis rates do not differ between lean and obese middle-aged men. Postprandial protein handling, including protein digestion and amino acid absorption, and the postprandial muscle protein synthetic response after the ingestion of 25 g whey protein are not impaired in obese men. This trial was registered at www.trialregister.nl as NTR4060.

Obesity Alters the Muscle Protein Synthetic Response to Nutrition and Exercise.

Improving the health of skeletal muscle is an important component of obesity treatment. Apart from allowing for physical activity, skeletal muscle tissue is fundamental for the regulation of postprandial macronutrient metabolism, a time period that represents when metabolic derangements are most often observed in adults with obesity. In order for skeletal muscle to retain its capacity for physical activity and macronutrient metabolism, its protein quantity and composition must be maintained through the efficient degradation and resynthesis for proper tissue homeostasis. Life-style behaviors such as increasing physical activity and higher protein diets are front-line treatment strategies to enhance muscle protein remodeling by primarily stimulating protein synthesis rates. However, the muscle of individuals with obesity appears to be resistant to the anabolic action of targeted exercise regimes and protein ingestion when compared to normal-weight adults. This indicates impaired muscle protein remodeling in response to the main anabolic stimuli to human skeletal muscle tissue is contributing to poor muscle health with obesity. Deranged anabolic signaling related to insulin resistance, lipid accumulation, and/or systemic/muscle inflammation are likely at the root of the anabolic resistance of muscle protein synthesis rates with obesity. The purpose of this review is to discuss the impact of protein ingestion and exercise on muscle protein remodeling in people with obesity, and the potential mechanisms underlining anabolic resistance of their muscle.

Leucine Co-Ingestion Augments the Muscle Protein Synthetic Response to the Ingestion of 15 g Protein During Recovery from Resistance Exercise in Older Men

Leucine Co-Ingestion Augments the Muscle Protein Synthetic Response to the Ingestion of 15 g Protein During Recovery from Resistance Exercise in Older Men

Anabolic Signaling Phosphorylation Does Not Explain Differential Muscle Protein Synthesis with Intra-Set Rest Manipulation

Power development is imperative for dynamic sport athletes. Cluster sets (CLU) are an effective method to allay the progressive decrement in power output normally observed in a traditional (TRD) resistance exercise strategy. CLU configurations incorporate a brief intra-set rest period to preserve velocity and power. Despite favorable performance, we previously established that TRD configurations elicit higher myofibrillar protein synthesis (MPS) rates when compared to CLU. However, it remains unclear if hallmark readouts related to mTORC1-signaling underlie this observation. PURPOSE: To elucidate anabolic signaling mechanisms driving differential MPS rates observed between CLU and TRD paradigms of the barbell back squat in trained men and women. METHODS: In randomized crossover design, 8 resistance-trained adults (7M, 1F; 23 ± 4 y; LBM, 63 ± 9 kg; back squat 1RM, 150 ± 26 kg) performed an acute bout of either CLU (4 sets × (2 × 5) repetitions, 30s intra-set rest, 90s inter-set rest) or TRD (4 sets × 10 repetitions, 120s inter-set rest) barbell back squats at ~70% 1RM. Volume load and total rest were matched between bouts. Participants ingested 20g of whey protein immediately before and after exercise. Muscle biopsies were collected at rest and at 0, 2, and 5 h post-exercise during primed-continuous L-[ring-13C6]phenylalanine infusions. Total and phosphorylated states of targeted proteins were assessed through immunoblotting. Data was normalized to an internal loading control. RESULTS: The phosphorylation of focal adhesion kinase (FAK) was doubled with TRD, but not significantly different, from CLU (TRD 2.1 ± 0.9-fold increase from baseline; CLU 1.3 ± 0.9-fold; p>0.05). Downstream targets of mTORC1 also showed no differences in phosphorylation between paradigms (4E-BP1: TRD 1.6 ± 0.3-fold, CLU 0.4 ± 0.2-fold; p706SK: TRD 1.5 ± 0.4-fold, CLU 0.9 ± 0.4-fold). Similarly, there was no difference in AMPK phosphorylation between conditions (TRD 1.3 ± 0.9-fold; CLU 0.9 ± 0.7-fold). CONCLUSION: Our data demonstrated that changes in protein phosphorylation as noted by various readouts within the mTORC1 pathway do not underpin the greater post-exercise muscle protein synthetic response with TRD versus CLU-style in resistance trained men and women.

Leucine coingestion augments the muscle protein synthetic response to the ingestion of 15 g of protein following resistance exercise in older men.

Older adults have shown an attenuated postexercise increase in muscle protein synthesis rates following ingestion of smaller amounts of protein compared with younger adults. Consequently, it has been suggested that older adults require the ingestion of more protein to increase postexercise muscle protein synthesis rates compared with younger adults. We investigated whether coingestion of 1.5 g of free leucine with a single 15-g bolus of protein further augments the postprandial muscle protein synthetic response during recovery from resistance-type exercise in older men. Twenty-four healthy older men (67 ± 1 yr) were randomly assigned to ingest 15 g of milk protein concentrate (MPC80) with (15G+LEU; n = 12) or without (15G; n = 12) 1.5 g of free leucine after performing a single bout of resistance-type exercise. Postprandial protein digestion and amino acid absorption kinetics, whole body protein metabolism, and postprandial myofibrillar protein synthesis rates were assessed using primed, continuous infusions with l-[ring-2H5]phenylalanine, l-[ring-2H2]tyrosine, and l-[1-13C]leucine combined with ingestion of intrinsically l-[1-13C]phenylalanine-labeled milk protein. A total of 70 ± 1% (10.5 ±0.2 g) and 75 ± 2% (11.2 ± 0.3 g) of the protein-derived amino acids were released in the circulation during the 6-h postexercise recovery phase in 15G+LEU and 15G, respectively (P < 0.05). Postexercise myofibrillar protein synthesis rates were 16% (0.058 ± 0.003 vs. 0.049 ± 0.002%/h, P < 0.05; based on l-[ring-2H5]phenylalanine) and 19% (0.071 ± 0.003 vs. 0.060 ± 0.003%/h, P < 0.05; based on l-[1-13C]leucine) greater in 15G+LEU compared with 15G. Leucine coingestion further augments the postexercise muscle protein synthetic response to the ingestion of a single 15-g bolus of protein in older men.

Skeletal Muscle Protein Synthetic Response to Amino Acid and Peptides

Skeletal Muscle Protein Synthetic Response to Amino Acid and Peptides

Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trial.

BackgroundAn inadequate protein intake may offset the muscle protein synthetic response after physical activity, reducing the possible benefits of an active lifestyle for muscle mass. We examined the effects of 12 weeks of daily protein supplementation on lean body mass, muscle strength, and physical performance in physically active older adults with a low habitual protein intake (<1.0 g/kg/day).MethodsA randomized double‐blinded controlled trial was performed among 116 physically active older adults [age 69 (interquartile range: 67–73) years, 82% male] who were training for a 4 day walking event of 30, 40, or 50 km/day. Participants were randomly allocated to either 31 g of milk protein or iso‐caloric placebo supplementation for 12 weeks. Body composition (dual‐energy X‐ray absorptiometry), strength (isometric leg extension and grip strength), quadriceps contractile function, and physical performance [Short Physical Performance Battery, Timed Up‐and‐Go test, and cardiorespiratory fitness (Åstrand–Rhyming submaximal exercise test)] were measured at baseline and after 12 weeks. We assessed vitamin D status and markers of muscle damage and renal function in blood and urine samples before and after intervention.ResultsA larger increase in relative lean body mass was observed in the protein vs. placebo group (∆0.93 ± 1.22% vs. ∆0.44 ± 1.40%, P Interaction = 0.046). Absolute and relative fat mass decreased more in the protein group than in the placebo group (∆−0.90 ± 1.22 kg vs. ∆−0.31 ± 1.28 kg, P Interaction = 0.013 and ∆−0.92 ± 1.19% vs. ∆−0.39 ± 1.36%, P Interaction = 0.029, respectively). Strength and contractile function did not change in both groups. Gait speed, chair‐rise ability, Timed Up‐and‐Go, and cardiorespiratory fitness improved in both groups (P < 0.001), but no between‐group differences were observed. Serum urea increased in the protein group, whereas no changes were observed in the placebo group (P Interaction < 0.001). No between‐group differences were observed for vitamin D status, muscle damage, and renal function markers.ConclusionsIn physically active older adults with relatively low habitual dietary protein consumption, an improvement in physical performance, an increase in lean body mass, and a decrease in fat mass were observed after walking exercise training. A larger increase in relative lean body mass and larger reduction in fat mass were observed in participants receiving 12 weeks of daily protein supplementation compared with controls, whereas this was not accompanied by differences in improvements between groups in muscle strength and physical performance.

PI3K-AKT-FOXO1 pathway targeted by skeletal muscle microRNA to suppress proteolytic gene expression in response to carbohydrate intake during aerobic exercise.

Ingesting protein and carbohydrate together during aerobic exercise suppresses the expression of specific skeletal muscle microRNA and promotes muscle hypertrophy. Determining whether there are independent effects of carbohydrate and protein on microRNA will allow for a clearer understanding of the mechanistic role microRNA serve in regulating skeletal muscle protein synthetic and proteolytic responses to nutrition and exercise. This study determined skeletal muscle microRNA responses to aerobic exercise with or without carbohydrate, and recovery whey protein (WP). Seventeen males were randomized to consume carbohydrate (CHO; 145 g; n = 9) or non‐nutritive control (CON; n = 8) beverages during exercise. Muscle was collected before (BASE) and after 80 min of steady‐state exercise (1.7 ± 0.3 V̇O2 L·min−1) followed by a 2‐mile time trial (17.9 ± 3.5 min; POST), and 3‐h into recovery after consuming WP (25 g; REC). RT‐qPCR was used to determine microRNA and mRNA expression. Bioinformatics analysis was conducted using the mirPath software. Western blotting was used to assess protein signaling. The expression of six microRNA (miR‐19b‐3p, miR‐99a‐5p, miR‐100‐5p, miR‐222‐3p, miR‐324‐3p, and miR‐486‐5p) were higher (P < 0.05) in CHO compared to CON, all of which target the PI3K‐AKT, ubiquitin proteasome, FOXO, and mTORC1 pathways. p‐AKTT hr473 and p‐FOXO1Thr24 were higher (P < 0.05) in POST CHO compared to CON. The expression of PTEN was lower (P < 0.05) in REC CHO than CON, while MURF1 was lower (P < 0.05) POST CHO than CON. These findings suggest the mechanism by which microRNA facilitate skeletal muscle adaptations in response to exercise with carbohydrate and protein feeding is by inhibiting markers of proteolysis.