Philip J Atherton

University of Nottingham, Nottigham, England, United Kingdom

Are you Philip J Atherton?

Claim your profile

Publications (41)196.57 Total impact

  • Matthew S Brook · Daniel J Wilkinson · Kenneth Smith · Philip J Atherton
    [Show abstract] [Hide abstract]
    ABSTRACT: Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great importance for maintaining health and quality-of-life into older age, under conditions of cachectic disease and with rehabilitation. In healthy weight-bearing individuals, muscle mass is maintained by the equilibrium between muscle protein synthesis (MPS) and muscle protein breakdown; when this balance tips in favour of MPS hypertrophy occurs. Despite considerable research into pharmacological/nutraceutical interventions, resistance exercise training (RE-T) remains the most potent stimulator of MPS and hypertrophy (in the majority of individuals). However, the mechanism(s) and time course of hypertrophic responses to RE-T remain poorly understood. We would suggest that available data are very much in favour of the notion that the majority of hypertrophy occurs in the early phases of RE-T (though still controversial to some) and that, for the most part, continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy represent the culmination of mechanical, auto/paracrine and endocrine events, the measurement of MPS remains a cornerstone for understanding the control of hypertrophy - mainly because it is the underlying driving force behind skeletal muscle hypertrophy. Development of sophisticated isotopic techniques (i.e. deuterium oxide) that lend to longer term insight into the control of hypertrophy by sustained RE-T will be paramount in providing insights into the metabolic and temporal regulation of hypertrophy. Such technologies will have broad application in muscle mass intervention for both athletes and for mitigating disease/age-related cachexia and sarcopenia, alike.
    08/2015; DOI:10.1080/17461391.2015.1073362
  • [Show abstract] [Hide abstract]
    ABSTRACT: Resistance exercise training (RET) is widely used to increase muscle mass in athletes and also aged/cachectic populations. However, the time course and metabolic and molecular control of hypertrophy remain poorly defined. Using newly developed deuterium oxide (D2O)-tracer techniques, we investigated the relationship between long-term muscle protein synthesis (MPS) and hypertrophic responses to RET. A total of 10 men (23 ± 1 yr) undertook 6 wk of unilateral (1-legged) RET [6 × 8 repetitions, 75% 1 repetition maximum (1-RM) 3/wk], rendering 1 leg untrained (UT) and the contralateral, trained (T). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom percentage; thereafter 50 ml/wk) with regular body water monitoring in saliva via high-temperature conversion elemental analyzer:isotope ratio mass spectrometer. Further bilateral VL muscle biopsies were taken at 3 and 6 wk to temporally quantify MPS via gas chromatography:pyrolysis:isotope ratio mass spectrometer. Expectedly, only the T leg exhibited marked increases in function [i.e., 1-RM/maximal voluntary contraction (60°)] and VL thickness (peaking at 3 wk). Critically, whereas MPS remained unchanged in the UT leg (e.g., ∼1.35 ± 0.08%/d), the T leg exhibited increased MPS at 0-3 wk (1.6 ± 0.01%/d), but not at 3-6 wk (1.29 ± 0.11%/d); this was reflected by dampened acute mechanistic target of rapamycin complex 1 signaling responses to RET, beyond 3 wk. Therefore, hypertrophic remodeling is most active during the early stages of RET, reflecting longer-term MPS. Moreover, D2O heralds promise for coupling MPS and muscle mass and providing insight into the control of hypertrophy and efficacy of anabolic interventions.-Brook, M. S., Wilkinson, D. J., Mitchell, W. K., Lund, J. N., Szewczyk, N. J., Greenhaff, P. L., Smith, K., Atherton, P. J. Skeletal muscle hypertrophy adaptations predominate in the early stages of resistance exercise training, matching deuterium oxide-derived measures of muscle protein synthesis and mechanistic target of rapamycin complex 1 signaling. © FASEB.
    The FASEB Journal 07/2015; DOI:10.1096/fj.15-273755 · 5.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood e.g. after intake of "slow" or "fast" protein sources or in response to grazing vs. bolus feeding-patterns may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood-flow, anabolic signalling and muscle protein synthesis (MPS) in older men. Sixteen men (~70y) consumed (EAA) either as a single dose (BOLUS; 15g; n=8) or as small repeated fractions (PULSE; 4x3.75g every 45-min; n=8) during 13C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic-signalling and MPS. Muscle blood-flow was assessed by contrast enhanced ultrasound (Sonovue™). BOLUS achieved rapid insulinemia (12.7 µiU.mL(-1); 25-min post-feed), essential aminoacidemia (~3000 µM 45-65 min post-feed) and mTORC1 activity; PULSE achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (~1800 µM 80-195 min after feeding) and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSR's of 0.051, 0.047%.h(-1) (BOLUS, PULSE) increased to 0.084, 0.073 %.h(-1) respectively. Moreover, PULSE led to sustainment of MPS beyond 180 min, when BOLUS MPS had returned to basal rates. We detected no benefit of rapid aminoacidemia in this older population despite enhanced anabolic signalling and greater overall EAA exposure. Rather, apparent delayed onset of the "muscle-full" effect permitted identical MPS following low-amplitude sustained EAA exposure. Copyright © 2015, American Journal of Physiology - Endocrinology and Metabolism.
    AJP Endocrinology and Metabolism 07/2015; DOI:10.1152/ajpendo.00112.2015 · 4.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stable isotope tracer methodologies are becoming increasingly widespread in metabolic research; yet a number of factors restrict their implementation, such as, i.v infusions, multiple cannulae, tissue samples, and significant cost. We recently validated the sensitivity of the orally administered stable isotope tracer deuterium oxide (D2O) for quantifying day-to-day changes in muscle protein synthesis (MPS). This method is less invasive, restrictive, and more cost-effective than traditional amino acid (AA) tracer techniques. In the present study, we hypothesized the sensitivity of our analytical techniques (GC-Pyrolysis-IRMS) would permit D2O-derived measurements of MPS over much shorter periods (i.e., hours) usually only possible using AA-tracer techniques. We recruited nine males (24 ± 3 year, BMI: 25 ± 3 kg·m(-)²) into an internally controlled comparison of D2O versus (13)C AA-tracers. The day before the acute study subjects consumed 400 mL D2O, and on the study day, received a primed (0.3 mg·kg(-1)) continuous (0.6 mg·kg·h(-1)) i.v infusion of L-[ring-(13)C6]-phenylalanine to quantify MPS under both: (1) basal [postabsorptive] and; (2) stimulated [postprandial] that is, consumption of 20 g EAA, conditions. Measures of MPS yielded indistinguishable technique differences with respect to EAA, (13)C: 0.065 ± 0.004 to 0.089 ± 0.006%·h(-1) (P < 0.05) and D2O: 0.050 ± 0.007 to 0.088 ± 0.008%·h(-1) (P < 0.05) with qualitatively similar increases. Our findings reveal that acute measurement of MPS, usually only possible using AA-tracers, are feasible over shorter periods with orally administered D2O when used in tandem with GC-Pyrolysis-IRMS. We conclude that this D2O approach provides a less invasive, cost-effective, and flexible means by which to quantify MPS acutely over several hours. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    07/2015; 3(7). DOI:10.14814/phy2.12433
  • Source
    AJP Endocrinology and Metabolism 05/2015; 308(9):E847. DOI:10.1152/ajpendo.00581.2014 · 4.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The anabolic effects of dietary protein on skeletal muscle depend on adequate skeletal muscle perfusion, which is impaired in older people. To explore fed-state muscle microvascular blood flow, protein metabolism and exercise-training status in older men. We measured leg blood flow (LBF), muscle microvascular blood volume (MBV) and muscle protein turnover under postabsorptive and fed-state (IV Glamin to double AA, dextrose to sustain glucose ∼7-7.5 mmol·l(-1) ) conditions in two groups: 10 untrained men (72.3 ± 1.4 y; BMI 26.5 ± 1.15 kg·m(2) ) and 10 men who had undertaken 20-weeks fully-supervised, whole-body resistance-exercise training (RET) (72.8 ± 1.4 y; BMI 26.3 ± 1.2 kg·m(2) ). We measured LBF by Doppler ultrasound and muscle MBV by contrast enhanced ultrasound (CEUS). Muscle protein synthesis (MPS) was measured using [1, 2-(13) C2 ] leucine with breakdown (MPB) and net protein balance (NPB) by ring-[D5 ] phenylalanine tracers. Plasma insulin was measured via ELISA and indices of anabolic signalling (e.g. Akt/mTORC1) by immunoblotting from muscle biopsies. Whereas older untrained men did not exhibit fed-state increases in LBF or MBV, the RET group exhibited increases in both LBF and MBV. Despite our hypothesis that enhanced fed-state circulatory responses would improve anabolic responses to nutrition, fed-sate increases in MPS (∼50-75%; P<0.001), were identical in both groups. Finally, whereas only the RET group exhibited fed-state suppression of MPB (∼-38%; P<0.05), positive net protein balance (NPB) achieved was similar in both groups. We conclude that RET enhances fed-state LBF and MBV and restores nutrient-dependent attenuation of MPB without robustly enhancing MPS or NPB. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Journal of Physiology 04/2015; 593(12). DOI:10.1113/JP270343 · 4.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dysregulated anabolic responses to nutrition/exercise may contribute to sarcopenia; however, these characteristics are poorly defined in female populations. We determined the effects of two-feeding regimes in older women (66±2.5y N=8/group): bolus-whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) (LEAA-3g [40% leucine]). Using (13)C6-Phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and both in response to feeding (FED) and feeding-plus-exercise (FED-EX; RE: 6×8 knee-extensions at 75%-1RM). We also quantified plasma insulin/AA concentrations, whole-leg (LBF)/muscle microvascular blood-flow (MBF), and muscle anabolic signaling by phospho-immunoblotting. Plasma insulinemia and EAA-aemia were markedly greater after WP than LEAA (P<0.001). Neither LEAA nor WP modified LBF in response to FED or FED-EX, while MBF increased to a similar extent in both groups, only after FED-EX (P<0.05). In response to FED, both WP and LEAA equally stimulated MPS 0-2h (P<0.05), abating thereafter (0-4h; P>0.05). In contrast, after FED-EX, MPS increased 0-2h and remained elevated 0-4h (P<0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70S6K1(Thr389) increased after FED-EX (2h; P<0.05). APS increased similarly after WP and LEAA. Older women remain subtly responsive to nutrition±exercise. Intriguingly though, bolus-WP offers no trophic advantage over LEAA. Copyright © 2015, American Journal of Physiology - Endocrinology and Metabolism.
    AJP Endocrinology and Metabolism 03/2015; 308(12):ajpendo.00481.2014. DOI:10.1152/ajpendo.00481.2014 · 4.09 Impact Factor
  • Source
  • Journal of Applied Physiology 02/2015; 118(4):498-498. · 3.43 Impact Factor
  • Source
    Philip J. Atherton · Paul L. Greenhaff
    The Journal of Physiology 02/2015; 593(3). DOI:10.1113/jphysiol.2014.288373 · 4.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The anabolic response of skeletal muscle to essential amino acids (EAAs) is dose dependent, maximal at modest doses, and short lived, even with continued EAA availability, a phenomenon termed “muscle-full.” However, the effect of EAA ingestion profile on muscle metabolism remains undefined. Objective: We determined the effect of Bolus vs. Spread EAA feeding in young men and hypothesized that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism. Methods: We provided 16 young healthy men with 15 g mixed-EAA, either as a single dose (“Bolus” n = 8) or in 4 fractions at 45-min intervals (“Spread” n = 8). Plasma insulin and EAA concentrations were assayed by ELISA and ion-exchange chromatography, respectively. Limb blood flow by was determined by Doppler ultrasound, muscle microvascular flow by Sonovue (Bracco) contrast-enhanced ultrasound, and phosphorylation of mammalian target of rapamycin complex 1 substrates by immunoblotting. Intermittent muscle biopsies were taken to quantify myofibrillar-bound 13C6-phenylalanine to determine muscle protein synthesis (MPS). Results: Bolus feeding achieved rapid insulinemia (13.6 μIU ⋅ mL−1, 25 min after commencement of feeding), aminoacidemia (∼2500 μM at 45 min), and capillary recruitment (+45% at 45 min), whereas Spread feeding achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (peak: ∼1500 μM at 135 min), and no detectable capillary recruitment (all P < 0.01 vs. Bolus). Despite these differences, identical anabolic responses were observed; fasting fractional synthetic rates of 0.054% ⋅ h−1 (Bolus) and 0.066% ⋅ h−1 (Spread) increased to 0.095% and 0.104% ⋅ h−1 (no difference in increment or final values between regimens). With both Spread and Bolus feeding strategies, a latency of at least 90 min was observed before an upswing in MPS was evident. Similarly with both feeding strategies, MPS returned to fasting rates by 180 min despite elevated circulating EAAs. Conclusion: These data do not support EAA delivery profile as an important determinant of anabolism in young men at rest, nor rapid aminoacidemia/leucinemia as being a key factor in maximizing MPS. This trial was registered at clinicaltrials.gov as NCT01735539.
    Journal of Nutrition 01/2015; 145(2):jn. 114.199604. DOI:10.3945/jn.114.199604 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with a gradual loss of muscle mass termed sarcopenia, which has significant impact on quality-of-life. Because oxidative stress is proposed to negatively impact upon musculoskeletal aging, we investigated links between human aging and markers of oxidative stress, and relationships to muscle mass and strength in young and old nonsarcopenic and sarcopenic adults. Sixteen young and 16 old males (further subdivided into "old" and "old sarcopenic") were studied. The abundance of protein carbonyl adducts within skeletal muscle sarcoplasmic, myofibrillar, and mitochondrial protein subfractions from musculus vastus lateralis biopsies were determined using Oxyblot immunoblotting techniques. In addition, concentrations of recognized cytoprotective proteins (eg, heat shock proteins [HSP], αβ-crystallin) were also assayed. Aging was associated with increased mitochondrial (but not myofibrillar or sarcoplasmic) protein carbonyl adducts, independently of (stage-I) sarcopenia. Correlation analyses of all subjects revealed that mitochondrial protein carbonyl abundance negatively correlated with muscle strength ([1-repetition maximum], p = .02, r (2) = -.16), but not muscle mass (p = .13, r (2) = -.08). Abundance of cytoprotective proteins, including various HSPs (HSP 27 and 70), were unaffected by aging/sarcopenia. To conclude, these data reveal that mitochondrial protein carbonylation increases moderately with age, and that this increase may impact upon skeletal muscle function, but is not a hallmark of (stage-I) sarcopenia, per se.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2014; 70(2). DOI:10.1093/gerona/glu007 · 4.98 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Muscle hypertrophy following resistance training (RT) involves activation of myofibrillar protein synthesis (MPS) to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE) in untrained men (n = 23) and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index = 26.4±0.9 kg•m(2)) underwent a primed constant infusion of L-[ring-(13)C6] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (P<0.001) above rest 60-180 min post-exercise and 184±28% (P = 0.037) 180-360 min post exercise. Quadriceps volume increased 7.9±1.6% (-1.9-24.7%) (P<0.001) after training. There was no correlation between changes in quadriceps muscle volume and acute rates of MPS measured over 1-3 h (r = 0.02), 3-6 h (r = 0.16) or the aggregate 1-6 h post-exercise period (r = 0.10). Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05) with phosphorylation of 4E-BP1(Thr37/46) at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.
    PLoS ONE 02/2014; 9(2):e89431. DOI:10.1371/journal.pone.0089431 · 3.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated architectural, functional, and molecular responses of human skeletal muscle to concentric (CON) or eccentric (ECC) resistance training (RT). Twelve young males performed 10 weeks of concentric (CON) or eccentric (ECC) resistance training (RT) (n = 6 CON, 6 ECC). An additional 14 males were recruited to evaluate acute muscle fascicle behaviour and molecular signalling in biopsies collected from vastus lateralis (VL) after 30 min of single bouts of CON or ECC exercise. VL volume was measured by magnetic resonance imaging. Muscle architecture (fascicle length, Lf; pennation angle, PA) was evaluated by ultrasonography. Muscle remodelling signals to CON or ECC loading (MAPK/AKT-mammalian target of rapamycin (mTOR) signalling) and inflammatory pathway (TNFα/Murf-1-MAFbx) were evaluated by immunoblotting. Despite the ~1.2 fold greater load of the ECC group, similar increases in muscle volume (+8% CON and +6% ECC) and in maximal voluntary isometric contraction (+9% CON and +11% ECC) were found after RT. However, increases in Lf were greater after ECC than CON (+12 vs. +5%) while increases in PA were greater in CON than ECC (+30 vs. +5%). Distinct architectural adaptations were associated with preferential growth in the distal regions of VL for ECC (+ECC +8% vs. +CON +2) and mid-belly for CON (ECC +7 vs. CON +11%). While MAPK activation (p38MAPK, ERK1/2, p90RSK) was specific to ECC, neither mode affected AKT-mTOR or inflammatory signalling 30 min after exercise. Muscle growth with CON and ECC RT occurs with different morphological adaptations reflecting distinct fibre fascicle behaviour and molecular responses. This article is protected by copyright. All rights reserved.
    Acta Physiologica 01/2014; 210(3). DOI:10.1111/apha.12225 · 4.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Quantification of muscle protein synthesis (MPS) remains a cornerstone to understanding the control of muscle mass. Traditional (13)C-amino-acid tracer methodologies necessitate sustained bed-rest and intravenous cannulation(s), restricting studies to ~12h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, ageing and disease while querying the utility of tracer-techniques to predict the long-term efficacy of anabolic/anti-catabolic interventions. We tested the efficacy of the D2O tracer for quantifying MPS over a period not feasible with (13)C tracers and too short to quantify changes in mass. Eight men (22±3.5y) undertook one-legged resistance-exercise over 8-d (4×8-10 repetitions: 80%-1RM every second-day, to yield 'non-exercised' vs. 'exercise' leg-comparisons) with Vastus Lateralis biopsies taken bi-laterally: 0, 2, 4 and 8-days. After day-0 biopsies, participants consumed a D2O bolus (150ml; 70-Atom%); saliva was collected daily. Fractional synthetic rates (FSR) of myofibrillar (MyoPS), sarcoplasmic (SPS) and collagen (CPS) protein-fractions were measured by GC-Pyrolysis-IRMS and TC/EA-IRMS. Body-water initially enriched at 0.16-0.24 APE, decayed at ~0.009%.d-1. In the non-exercised-leg, MyoPS was: 1.45±0.10%.d-1, 1.47±0.06%.d(-1), 1.35±0.07%.d-1 at 0-2, 0-4 and 0-8d respectively (~0.05-0.06%.h-1). MyoPS was greater in the exercised-leg (0-2d 1.97±0.13%.d(-1), 0-4d 1.96±0.15%.d-1; P<0.01, 0-8d 1.79±0.12%.d(-1); P<0.05). CPS was slower than MyoPS, but followed a similar pattern, with the exercised-leg tending to yield greater FSR's (0-2d; 1.14±0.13%.d-1 vs. 1.45±0.15%.d(-1), 0-4d; 1.13±0.07%.d(-1) vs. 1.47±0.18%.d(-1), 0-8d; 1.03±0.09%.d(-1) vs. 1.40±0.11%.d(-1)). SPS remained unchanged. Therefore, D2O has unrivaled utility to quantify day-to-day MPS in humans and inform on short-term changes in anabolism, and presumably, catabolism alike.
    AJP Endocrinology and Metabolism 12/2013; 306(5). DOI:10.1152/ajpendo.00650.2013 · 4.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Skeletal muscle anabolism associated with postprandial plasma aminoacidaemia and insulinaemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesised that increasing muscle microvascular blood volume [flow] would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2±2.1 y) under postabsorptive and fed (I.V Glamin® (~10 g AA), glucose ~7.5 mmol·l(-1))) conditions. Methacholine was infused into the femoral artery of one-leg to determine, via bilateral comparison, the effects of feeding alone versus 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 modelling) and net protein balance (NPB) using [1,2-(13)C2] leucine and [D5] phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indices of anabolic-signalling/endothelial activation (e.g. Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12±5%, P<0.05), MBV (+25±10%, P<0.05) and MPS (+129±33%, P<0.05) increased. Infusion of methacholine further enhanced LBF (+126±12%, P<0.05) and MBV (+79±30%, P<0.05). In-spite of these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04±0.004 vs. 0.08±0.01%·h(-1), P<0.05) nor improvements in NPB (-9.7±4.8 vs. 34.2±14.1 nmol·min(-1), P<0.05) were affected by methacholine infusion (MPS 0.07±0.01%·h(-1); NPB 50.6±15.5 nmol·min(-1)), 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.
    AJP Endocrinology and Metabolism 11/2013; 306(2). DOI:10.1152/ajpendo.00440.2013 · 4.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Compromised limb blood flow in aging may contribute to the development of sarcopenia, frailty, and the metabolic syndrome. We developed a novel contrast-enhanced ultrasound technique using Sonovue™ to characterize muscle microvasculature responses to an oral feeding stimulus (15 g essential amino acids) in young (∼20 years) and older (∼70 years) men. Intensity-time replenishment curves were made via an ultrasound probe "fixed" over the quadriceps, with intermittent high mechanical index destruction of microbubbles within muscle vasculature. This permitted real-time measures of microvascular blood volume (MBV), microvascular flow velocity (MFV) and their product, microvascular blood flow (MBF). Leg blood flow (LBF) was measured by Doppler and insulin by enzyme-linked immunosorbent assay. Steady-state contrast concentrations needed for comparison between different physiological states were achieved <150 sec from commencing Sonovue™ infusion, and MFV and MBV measurements were completed <120 sec thereafter. Interindividual coefficients of variation in MBV and MFV were 35-40%, (N = 36). Younger men (N = 6) exhibited biphasic vascular responses to feeding with early increases in MBV (+36%, P < 0.008 45 min post feed) reflecting capillary recruitment, and late increases in MFV (+77%, P < 0.008) and MBF (+130%, P < 0.007 195 min post feed) reflecting more proximal vessel dilatation. Early MBV responses were synchronized with peak insulin but not increased LBF, while later changes in MFV and MBF occurred with insulin at post absorptive values but alongside increased LBF. All circulatory responses were absent in old men (N = 7). Thus, impaired postprandial circulation could impact age-related declines in muscle glucose disposal, protein anabolism, and muscle mass.
    10/2013; 1(5):e00119. DOI:10.1002/phy2.119
  • Philip James Atherton
    [Show abstract] [Hide abstract]
    ABSTRACT: Although nutritional requirements for warfighters will inevitably vary in accordance with job role and active-inactive duty cycling, somewhat generic recommendations do still apply. In considering aspects of "optimal" nutrient timing, it is important to outline singular and combinatorial relationships between protein intake and physical activity (e.g., exercise) in the context of the following: 1) skeletal muscle protein turnover, 2) functional recovery, and 3) adaptation to exercise. The essential amino acid (EAA) components of dietary protein are key macronutrients regulating muscle proteostasis, because they provide substrate to replenish muscle proteins lost during fasted periods. This occurs through a substantial, albeit short-lived (∼2 h) EAA-induced stimulation of muscle protein synthesis (MPS) and via an insulin-mediated suppression of muscle protein breakdown (MPB) (via carbohydrate- and/or EAA-mediated insulin secretory effects). At rest, intake of protein (optimal range between 20 and 40 g of high-quality protein, equating to ∼10-20 g EAAs) every ∼4-5 h is advocated due to the refractoriness of MPS in response to continuous supply. Bouts of exercise also stimulate muscle protein turnover (increasing both MPS and MPB), but in the absence of protein intake net muscle protein balance remains negative such that exercise alone is catabolic. Intake of dietary protein redresses this balance through enhancing both the amplitude and duration of exercise-induced increases in MPS while concomitantly limiting MPB. These postexercise periods of positive net protein balance permit muscle adaptation and functional recovery. Finally, in relation to exercise, protein dosing (at a minimum of ∼20 g) both in close proximity to exercise and thereafter every 4-5 h during waking hours (including before bedtime) is likely optimal for adaptation/functional recovery.
    Journal of Nutrition 09/2013; 143. DOI:10.3945/jn.113.175984 · 4.23 Impact Factor
  • Source

Publication Stats

970 Citations
196.57 Total Impact Points

Institutions

  • 2008–2015
    • University of Nottingham
      • • School of Medicine
      • • School of Graduate Entry Medicine and Health
      • • School of Biomedical Sciences
      Nottigham, England, United Kingdom
  • 2009
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom