Muscle Protein Synthetic Responses to Exercise: Effects of Age, Volume, and Intensity

Kumar, Vinod; Atherton, Philip J.; Selby, Anna; Rankin, Debbie; Williams, John W; Smith, Kenneth; Hiscock, Natalie; Rennie, Michael J.

doi:10.1093/gerona/gls141

Cited by 112 publications

(122 citation statements)

References 30 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…For direct measurements of MPS, ϳ20 mg of muscle was used, as described previously (22). In brief, the muscle was homogenized in ice-cold homogenization buffer [50 mM Tris·,HCl pH 7.4, 50 mM NaF, 10 mM ␤-glycerophosphate disodium salt, 1 mM EDTA, 1 mM EGTA, 1 mM activated Na 3VO4 (all Sigma-Aldrich, Poole, UK)] and a complete protease inhibitor cocktail tablet (Roche, West Sussex, UK) at 10 l/g tissue.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

Phillips

Atherton

Varadhan

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

-Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 Ϯ 2.1 yr) under postabsorptive and fed [iv Glamin (ϳ10 g AA), glucose ϳ7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-13 C2] leucine and [ 2 H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (ϩ12 Ϯ 5%, P Ͻ 0.05), MBV (ϩ25 Ϯ 10%, P Ͻ 0.05), and MPS (ϩ129 Ϯ 33%, P Ͻ 0.05) increased. Infusion of methacholine further enhanced LBF (ϩ126 Ϯ 12%, P Ͻ 0.05) and MBV (ϩ79 Ϯ 30%, P Ͻ 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 Ϯ 0.004 vs. 0.08 Ϯ 0.01%/h, P Ͻ 0.05) nor improvements in NPB (Ϫ4.4 Ϯ 2.4 vs. 16.4 Ϯ 5.7 nmol Phe·100 ml leg Ϫ1 ·min Ϫ1 , P Ͻ 0.05) were affected by methacholine infusion (MPS 0.07 Ϯ 0.01%/h; NPB 24.0 Ϯ 7.7 nmol Phe·100 ml leg Ϫ1 ·min Ϫ1 ), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism. blood flow; protein metabolism; muscle SKELETAL MUSCLES SERVE CRUCIAL locomotory and postprandial metabolic [e.g., amino acid (AA) and glucose disposal] functions (52). Given such vital functions, understanding the control of nutrient delivery in the context of muscle metabolism is important. The day-to-day stability of muscle mass in healthy, habitually active individuals (not engaged in formal exercise training) is the result of a dynamic equilibrium in muscle protein turnover, whereby rates of muscle protein synthesis (MPS) are balanced with those of breakdown (MPB) (4, 27). This equilibrium depends on the postprandial supply of essential amino acid (EAA) components of dietary protein, which provide the substrate and "signal" to recoup postabsorptive muscle protein losses. This role of EAAs has been delineated in both human (8, 32, 36) and animal work (1, 2, 15).Before EAA can act either as substrates or signals for MPS, they must leave the bloodstream, transverse the interstitial fluid, and be transported into myocytes (12). Potentially, then, both delivery and transendothelial AA transport could be rate limiting for the uptake of circulating AA by muscle ...

show abstract

Section: Methodsmentioning

confidence: 99%

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

Phillips

Atherton

Varadhan

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Approximately 20mg of muscle tissue was used for measures of MPS, as previously described (Kumar et al 2012). In brief, the myofibrillar pellet was precipitated by homogenisation and centrifugation with the soluble myofibrillar protein then precipitated by perchloric acid.…”

Section: Muscle Protein Synthesis (Mps)mentioning

confidence: 99%

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

Phillips

Atherton

Varadhan

et al. 2016

Appl. Physiol. Nutr. Metab.

View full text Add to dashboard Cite

show abstract

“…Skeletal muscle contractile activity plays a key role in the control of protein synthesis. Specifically, increased muscle contractile activity promotes increased protein synthesis, whereas muscle inactivity results in decreased rates of protein synthesis (13,54). The initial decrease in diaphragm protein synthesis that occurs during full support MV is likely due to decreased protein translation because myosin heavy chain mRNA levels remain unchanged (99,120).…”

Section: Mv-induced Decreases In Protein Diaphragmatic Synthesismentioning

confidence: 99%

Ventilator-induced diaphragm dysfunction: cause and effect

Powers

Wiggs

Sollanek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

143

156

View full text Add to dashboard Cite

Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol 305: R464 -R477, 2013. First published July 10, 2013 doi:10.1152/ajpregu.00231.2013 is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). This is significant because VIDD is thought to contribute to problems in weaning patients from the ventilator. Extended time on the ventilator increases health care costs and greatly increases patient morbidity and mortality. Research reveals that only 18 -24 h of MV is sufficient to develop VIDD in both laboratory animals and humans. Studies using animal models reveal that MV-induced diaphragmatic atrophy occurs due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems. respiratory muscle; atrophy; mechanical ventilation; weaning; muscle wasting MECHANICAL VENTILATION (MV) is used clinically to achieve sufficient pulmonary gas exchange in patients unable to sustain adequate alveolar ventilation on their own. Common indications for MV include respiratory failure due to chronic obstructive pulmonary disease, status asthmaticus, and/or heart failure. In addition, MV is often an essential intervention in patients suffering from acute drug overdose, neuromuscular diseases, sepsis, and during surgery along with postsurgical recovery.The number of patients receiving prolonged MV in the United States exceeds more than 300,000 each year in the intensive care unit (ICU) (20). Although MV can be a lifesaving measure, prolonged MV results in the rapid development of diaphragmatic weakness due to both atrophy and contractile dysfunction. This detrimental impact of prolonged MV on the diaphragm has been termed ventilator-induced diaphragmatic dysfunction (VIDD) and VIDD is predicted to be a major contributor to problems in weaning patients from the ventilator (26, 114). Although previous reports describing the impact of prolonged MV on the diaphragm have appeared in the literature, advances in our understanding of the mechanisms responsible for VIDD h...

show abstract

Muscle Protein Synthetic Responses to Exercise: Effects of Age, Volume, and Intensity

Cited by 112 publications

References 30 publications

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

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

Ventilator-induced diaphragm dysfunction: cause and effect

Contact Info

Product

Resources

About