Resistance Exercise Does Not Up-Regulate YAP Expression in Aged Human Skeletal Muscle

Abstract Objectives Yes-Associated Protein (YAP) is implicated as a regulator of the post-exercise skeletal muscle response through mechanical transduction. We recently observed that resistance exercise (RE) increased both total (t) and phosphorylated (p) muscle YAP content, which correlated with extracellular signal-regulated kinase 1/2 (Erk1/2). Other anabolic signaling pathways (i.e., mTORC1) are known to be potentiated by the combined stimuli of RE and protein ingestion during post-exercise recovery. However, the impact of protein ingestion on t- and p-muscle YAP content during recovery from RE is unknown. Therefore, we aimed to determine the nutrient sensitivity of YAP in both an acute and chronic exercise setting in aging skeletal muscle. Methods Acute study: 13 untrained older women (59.8 ± 0.5 y) were randomized to perform an acute bout of unilateral RE (3 sets × 12 repetitions at 65% of one repetition maximum) followed by the ingestion of whey protein (0.3 g/kg lean body mass) or water. Muscle biopsies of both the rested and exercised legs were collected before and during the postprandial period. Chronic study: 20 untrained middle-aged men and women (47.5 ± 0.3 y) performed 3 weeks of whole body RE (3 d/wk) with moderate or high protein intake set at 1.2 g/kg/d or 1.6 g/kg/d, respectively. Muscle biopsies were taken weekly in the rested state. Total and phosphorylated YAPSer127 and Erk1/2Thr202/Tyr204 were examined by western blotting. Results Acute study: Protein ingestion decreased t- and p-YAP compared to the water condition in the non-exercised leg (main effect: P < 0.04). There was no change in t- or p-YAP, regardless of condition, in the exercised-leg throughout recovery (P = 0.88). There was no change in p/t ratio of Erk1/2 in the exercised or non-exercised leg. Chronic study: There was no change in either p- or t-YAP in moderate and high protein conditions throughout training (both, P > 0.05). There was a decrease in t-Erk1/2 irrespective of condition (P = 0.04). There was no change in p/t ratio of Erk1/2 throughout training. There was a significant correlation between t-Erk1/2 and t-YAP (r = 0.741 and P < 0.001). Conclusions Protein ingestion mediated an acute down-regulation of YAP in the postprandial-state. However, resistance training did not modulate YAP content in aged skeletal muscle tissue. Funding Sources Funded by Beef Checkoff. AFS is supported by CAPES-Brazil.

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Activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion

Applied Physiology Nutrition and Metabolism ◽

10.1139/h11-132 ◽

2012 ◽

Vol 37 (1) ◽

pp. 21-30 ◽

Cited By ~ 42

Author(s):

Michelle M. Farnfield ◽

Leigh Breen ◽

Kate A. Carey ◽

Andrew Garnham ◽

David Cameron-Smith

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Whey Protein ◽

Acute Exercise ◽

Mrna Translation ◽

Exercise Bout ◽

Older Men ◽

Protein Ingestion ◽

Older Subjects ◽

The Impact

Purpose: To investigate the impact of whey protein ingestion and resistance exercise training on the phosphorylation of mRNA translational signalling proteins in the skeletal muscle of young and old men. Methods: Sixteen healthy young (aged 18–25 years) and 15 healthy older men (aged 60–75 years) completed 12 weeks of resistance exercise and were randomly assigned to consume a whey protein (WPI) or placebo drink after each session. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of training. Results: All subjects significantly increased strength after following strength training. Phosphorylation of mTOR was significantly greater in the WPI groups compared with placebo for both younger and older subjects. Phosphorylation of p70S6K, eIF4G, and 4EBP1 was greater for older subjects consuming WPI. Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger subjects that had consumed WPI. Post-training, younger subjects demonstrated a similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the initial heightened phosphorylation of mTOR, p70S6K, rpS6, and eIF4G in older muscle to combined resistance exercise and WPI ingestion became less pronounced after repeated training sessions. Conclusions: In the untrained state, resistance exercise coupled with WPI increases the phosphorylation of proteins involved in mRNA translation compared with exercise alone. Post-training, WPI- and exercise-induced protein phosphorylation was reduced in older men, but not in younger men. Thus, strategies to induce hypertrophy should utilize protein and resistance training concurrently. Further investigations should delineate interventions that will maintain sensitivity to anabolic stimuli in older populations.

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Resistance exercise increases human skeletal muscle AS160/TBC1D4 phosphorylation in association with enhanced leg glucose uptake during postexercise recovery

Journal of Applied Physiology ◽

10.1152/japplphysiol.90562.2008 ◽

2008 ◽

Vol 105 (6) ◽

pp. 1967-1974 ◽

Cited By ~ 21

Author(s):

Hans C. Dreyer ◽

Micah J. Drummond ◽

Erin L. Glynn ◽

Satoshi Fujita ◽

David L. Chinkes ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Glucose Uptake ◽

Human Skeletal Muscle ◽

Fat Oxidation ◽

Whole Body ◽

Akt Phosphorylation ◽

Postexercise Recovery ◽

Male Subjects ◽

Muscle Biopsies

Akt substrate of 160 kDa (AS160/TBC1D4) is associated with insulin and contraction-mediated glucose uptake. Human skeletal muscle AS160 phosphorylation is increased during aerobic exercise but not immediately following resistance exercise. It is not known whether AS160 phosphorylation is altered during recovery from resistance exercise. Therefore, we hypothesized that muscle AS160/TBC1D4 phosphorylation and glucose uptake across the leg would be increased during recovery following resistance exercise. We studied 9 male subjects before, during, and for 2 h of postexercise recovery. We utilized femoral catheterizations and muscle biopsies in combination with indirect calorimetry and immunoblotting to determine whole body glucose and fat oxidation, leg glucose uptake, muscle AMPKα2 activity, and the phosphorylation of muscle Akt and AS160/TBC1D4. Glucose oxidation was reduced while fat oxidation increased (∼35%) during postexercise recovery ( P ≤ 0.05). Glucose uptake increased during exercise and postexercise recovery ( P ≤ 0.05). Akt phosphorylation was increased at 1 h and AMPKα2 activity increased at 2 h postexercise ( P ≤ 0.05). Phospho(Ser/Thr)-Akt substrate (PAS) phosphorylation (often used as a marker for AS160) was unchanged immediately postexercise and increased at 1 h ( P ≤ 0.05) and 2 h postexercise ( P = 0.07). The PAS antibody is not always specific for AS160/TBC1D4 and can detect proteins at a similar molecular weight. Therefore, we immunoprecipitated AS160/TBC1D4 and then blotted with the PAS antibody, which confirmed that PAS phosphorylation is occurring on AS160/TBC1D4. There was also a positive correlation between PAS phosphorylation and leg glucose uptake during recovery ( P < 0.05). We conclude that resistance exercise increases AS160/TBC1D4 phosphorylation in association with an increase in leg glucose uptake during postexercise recovery.

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Consumption of a High-Protein Meal Replacement Leads to Higher Fat Oxidation, Suppression of Hunger, and Improved Metabolic Profile After an Exercise Session

Nutrients ◽

10.3390/nu13010155 ◽

2021 ◽

Vol 13 (1) ◽

pp. 155

Author(s):

Camila L. P. Oliveira ◽

Normand G. Boulé ◽

Aloys Berg ◽

Arya M. Sharma ◽

Sarah A. Elliott ◽

...

Keyword(s):

Metabolic Profile ◽

Fat Oxidation ◽

High Protein ◽

Whole Body ◽

Moderate Intensity ◽

Exercise Session ◽

Meal Replacement ◽

Protein Meal ◽

High Protein Meal ◽

The Impact

The aim of this study was to compare the impact of a high-protein meal replacement (HP-MR) versus a control (CON) breakfast on exercise metabolism. In this acute, randomized controlled, cross-over study, participants were allocated into two isocaloric arms: (a) HP-MR: 30% carbohydrate, 43% protein, and 27% fat; (b) CON: 55% carbohydrate, 15% protein, and 30% fat. Following breakfast, participants performed a moderate-intensity aerobic exercise while inside a whole-body calorimetry unit. Energy expenditure, macronutrient oxidation, appetite sensations, and metabolic blood markers were assessed. Forty-three healthy, normal-weight adults (24 males) participated. Compared to the CON breakfast, the HP-MR produced higher fat oxidation (1.07 ± 0.33 g/session; p = 0.003) and lower carbohydrate oxidation (−2.32 ± 0.98 g/session; p = 0.023) and respiratory exchange ratio (−0.01 ± 0.00; p = 0.003) during exercise. After exercise, increases in hunger were lower during the HP-MR condition. Changes in blood markers from the fasting state to post-exercise during the HP-MR condition were greater for insulin, peptide tyrosine-tyrosine, and glucagon-like peptide 1, and lower for low-density lipoprotein cholesterol, triglyceride, and glycerol. Our primary findings were that an HP-MR produced higher fat oxidation during the exercise session, suppression of hunger, and improved metabolic profile after it.

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Presleep dietary protein-derived amino acids are incorporated in myofibrillar protein during postexercise overnight recovery

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00273.2016 ◽

2018 ◽

Vol 314 (5) ◽

pp. E457-E467 ◽

Cited By ~ 33

Author(s):

Jorn Trommelen ◽

Imre W. K. Kouw ◽

Andrew M. Holwerda ◽

Tim Snijders ◽

Shona L. Halson ◽

...

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Dietary Protein ◽

Myofibrillar Protein ◽

Whole Body ◽

Body Protein ◽

Protein Ingestion ◽

Casein Protein ◽

The Impact ◽

Myofibrillar Protein Synthesis

The purpose of this study was to determine the impact of ingesting 30 g casein protein with and without 2 g free leucine before sleep on myofibrillar protein synthesis rates during postexercise overnight recovery. Thirty-six healthy young men performed a single bout of resistance-type exercise in the evening (1945) after a full day of dietary standardization. Thirty minutes before sleep (2330), subjects ingested 30 g intrinsically l-[1-13C]phenylalanine-labeled protein with (PRO+leu, n = 12) or without (PRO, n = 12) 2 g free leucine, or a noncaloric placebo (PLA, n = 12). Continuous intravenous l-[ ring-2H5]phenylalanine, l-[1-13C]leucine, and l-[ ring-2H2]tyrosine infusions were applied. Blood and muscle tissue samples were collected to assess whole body protein net balance, myofibrillar protein synthesis rates, and overnight incorporation of dietary protein-derived amino acids into myofibrillar protein. Protein ingestion before sleep improved overnight whole body protein net balance ( P < 0.001). Myofibrillar protein synthesis rates did not differ significantly between treatments as assessed by l-[ ring-2H5]phenylalanine (0.057 ± 0.002, 0.055 ± 0.002, and 0.055 ± 0.004%/h for PLA, PRO, and PRO+leu, respectively; means ± SE; P = 0.850) or l-[1-13C]leucine (0.080 ± 0.004, 0.073 ± 0.004, and 0.083 ± 0.006%/h, respectively; P = 0.328). Myofibrillar l-[1-13C]phenylalanine enrichments increased following protein ingestion but did not differ between the PRO and PRO+leu treatments. In conclusion, protein ingestion before sleep improves whole body protein net balance and provides amino acids that are incorporated into myofibrillar protein during sleep. However, the ingestion of 30 g casein protein with or without additional free leucine before sleep does not increase muscle protein synthesis rates during postexercise overnight recovery.

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Antecubital Vein Cannula Position Impacts Assessment of Forearm Glucose Uptake During an Oral Glucose Challenge in Healthy Volunteers

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1275-4038 ◽

2020 ◽

Author(s):

Cécile Bétry ◽

Aline V. Nixon ◽

Paul L. Greenhaff ◽

Elizabeth J. Simpson

Keyword(s):

Skeletal Muscle ◽

Blood Glucose ◽

Glucose Uptake ◽

Venous Blood ◽

Whole Body ◽

Oral Glucose ◽

Antecubital Vein ◽

Glucose Challenge ◽

The Impact

Abstract Introduction Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure for assessing glucose uptake. However, the possibility of multiple tissues contributing to the composition of venous blood, and the differential in glucose uptake kinetics between tissue types, suggests that sampling from different vein sites could influence the estimation of glucose uptake. This study aimed to determine the impact of venous cannula position on calculated forearm glucose uptake following an oral glucose challenge in resting and post-exercise states. Materials and Methods In 9 young, lean, males, the impact of sampling blood from two antecubital vein positions; the perforating vein (‘perforating’ visit) and, at the bifurcation of superficial and perforating veins (‘bifurcation’ visit), was assessed. Brachial artery blood flow and arterialised-venous and venous blood glucose concentrations were measured in 3 physiological states; resting-fasted, resting-fed, and fed following intermittent forearm muscle contraction (fed-exercise). Results Following glucose ingestion, forearm glucose uptake area under the curve was greater for the ‘perforating’ than for the ‘bifurcation’ visit in the resting-fed (5.92±1.56 vs. 3.69±1.35 mmol/60 min, P<0.01) and fed-exercise (17.38±7.73 vs. 11.40±7.31 mmol/75 min, P<0.05) states. Discussion Antecubital vein cannula position impacts calculated postprandial forearm glucose uptake. These findings have implications for longitudinal intervention studies where serial determination of forearm glucose uptake is required.

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Resistance training reduces whole-body protein turnover and improves net protein retention in untrained young males

Applied Physiology Nutrition and Metabolism ◽

10.1139/h06-031 ◽

2006 ◽

Vol 31 (5) ◽

pp. 557-564 ◽

Cited By ~ 56

Author(s):

Joseph W. Hartman ◽

Daniel R. Moore ◽

Stuart M. Phillips

Keyword(s):

Resistance Training ◽

Resistance Exercise ◽

Nitrogen Balance ◽

Protein Turnover ◽

Whole Body ◽

Body Protein ◽

Protein Retention ◽

The Impact ◽

Net Protein ◽

Urinary Nitrogen

It is thought that resistance exercise results in an increased need for dietary protein; however, data also exists to support the opposite conclusion. The purpose of this study was to determine the impact of resistance exercise training on protein metabolism in novices with the hypothesis that resistance training would reduce protein turnover and improve whole-body protein retention. Healthy males (n = 8, 22 ± 1 y, BMI = 25.3 ± 1.8 kg·m–2) participated in a progressive whole-body split routine resistance-training program 5d/week for 12 weeks. Before (PRE) and after (POST) the training, oral [15N]-glycine ingestion was used to assess nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB), and net protein balance (NPB = PS – PB). Macronutrient intake was controlled over a 5d period PRE and POST, while estimates of protein turnover and urinary nitrogen balance (Nbal = Nin – urine Nout) were conducted. Bench press and leg press increased 40% and 50%, respectively (p < 0.01). Fat- and bone-free mass (i.e., lean muscle mass) increased from PRE to POST (2.5 ± 0.8 kg, p < 0.05). Significant PRE to POST decreases (p <0.05) occurred in Q (0.9 ± 0.1 vs. 0.6 ± 0.1 g N·kg–1·d–1), PS (4.6 ± 0.7 vs. 2.9 ± 0.3 g·kg–1·d–1), and PB (4.3 ± 0.7 vs. 2.4 ± 0.2 g·kg–1·d–1). Significant training-induced increases in both NPB (PRE = 0.22 ± 0.13 g·kg–1·d–1; POST = 0.54 ± 0.08 g·kg–1·d–1) and urinary nitrogen balance (PRE = 2.8 ± 1.7 g N·d–1; POST = 6.5 ± 0.9 g N·d–1) were observed. A program of resistance training that induced significant muscle hypertrophy resulted in reductions of both whole-body PS and PB, but an improved NPB, which favoured the accretion of skeletal muscle protein. Urinary nitrogen balance increased after training. The reduction in PS and PB and a higher NPB in combination with an increased nitrogen balance after training suggest that dietary requirements for protein in novice resistance-trained athletes are not higher, but lower, after resistance training.

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Alterations in Skeletal Muscle Repair in Young Adults with Type 1 Diabetes Mellitus

AJP Cell Physiology ◽

10.1152/ajpcell.00322.2021 ◽

2021 ◽

Author(s):

Athan G. Dial ◽

Grace K. Grafham ◽

Cynthia MF. Monaco ◽

Jennifer Voth ◽

Linda Brandt ◽

...

Keyword(s):

Electron Microscopy ◽

Skeletal Muscle ◽

Type 1 Diabetes ◽

Young Adults ◽

Gene Networks ◽

Vastus Lateralis ◽

Post Exercise ◽

Ultrastructural Damage ◽

The Impact

Though preclinical models of type 1 diabetes (T1D) exhibit impaired muscle regeneration, this has yet to be investigated in humans with T1D. Here we investigated the impact of damaging exercise (eccentric quadriceps contractions) in eighteen physically-active young adults with and without T1D. Pre- and post-exercise (48h and 96h), participants provided blood samples, vastus lateralis biopsies and performed maximal voluntary quadriceps contractions (MVC). Skeletal muscle sarcolemmal integrity, extracellular matrix content (ECM), and satellite cell (SC) content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage. MVC was comparable between T1D and controls before exercise. Post-exercise, MVC was decreased in both groups, but T1D subjects exhibited moderately lower strength recovery at both 48h and 96h. Serum creatine kinase, an indicator of muscle damage, was moderately higher in T1D participants at rest, and exhibited a small elevation 96h post-exercise. T1D participants showed lower SC content at all timepoints and demonstrated a moderate delay in SC proliferation after exercise. A greater number of myofibers exhibited sarcolemmal damage (disrupted dystrophin) and increased ECM (laminin) content in participants with T1D despite no differences between groups in ultrastructural damage as assessed by electron microscopy. Finally, transcriptomic analyses revealed dysregulated gene networks involving RNA translation and mitochondrial respiration, providing potential explanations for previous observations of mitochondrial dysfunction in similar T1D cohorts. Our findings indicate that skeletal muscle in young adults with moderately-controlled T1D is altered after damaging exercise; suggesting that longer recovery times following intense exercise may be necessary.

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The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery

Nutrients ◽

10.3390/nu12020280 ◽

2020 ◽

Vol 12 (2) ◽

pp. 280 ◽

Cited By ~ 7

Author(s):

Anne-Marie Lundsgaard ◽

Andreas M. Fritzen ◽

Bente Kiens

Keyword(s):

Skeletal Muscle ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Whole Body ◽

Tissue Blood Flow ◽

Peroxisome Proliferator ◽

Early Recovery ◽

Peroxisome Proliferator Activated Receptor ◽

Post Exercise ◽

Exercise Induced

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

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