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1.
Physiol Genomics ; 56(7): 506-518, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38766755

RESUMEN

Both sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction (SR), with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females. Ten healthy females aged 18-35 yr old undertook a randomized cross-over study of nine nights of SR (5 h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-wk washout. Participants completed four REx sessions per condition (days 3, 5, 7, and 9). Muscle biopsies were collected both pre- and post-REx on days 3 and 9. Gene and protein expression were assessed by RNA sequencing and Western blot, respectively. Three or nine nights of SR had no effect on the muscle transcriptome independently of exercise. However, close to 3,000 transcripts were differentially regulated (false discovery rate < 0.05) 48 h after the completion of three resistance exercise sessions in both NS and SR conditions. Only 39% of downregulated genes and 18% of upregulated genes were common between both conditions, indicating a moderating effect of SR on the response to exercise. SR and REx interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.NEW & NOTEWORTHY This study investigated the effect of nine nights of sleep restriction, with repeated resistance exercise sessions, on the skeletal muscle transcriptome of young, trained females. Sleep restriction and resistance exercise interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.


Asunto(s)
Estudios Cruzados , Músculo Esquelético , Entrenamiento de Fuerza , Privación de Sueño , Transcriptoma , Humanos , Femenino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Entrenamiento de Fuerza/métodos , Adulto Joven , Adulto , Transcriptoma/genética , Adolescente , Privación de Sueño/genética , Ejercicio Físico/fisiología , Regulación de la Expresión Génica , Perfilación de la Expresión Génica/métodos
2.
Nutrients ; 15(22)2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-38004115

RESUMEN

This research aimed to determine the effects of Gynostemma pentaphyllum (G. pentaphyllum) on exercise performance, AMP-activated protein kinase (AMPK), and mitochondrial signaling in human muscle. This randomized double-blind placebo control crossover study provided placebo or 450 mg of G. pentaphyllum dried leaf extract equivalent to 2.25 g of dry leaf per day for four weeks to 16 healthy untrained young males, separated by four weeks wash-out. Following 4-week supplementation with G. pentaphyllum, participants had significantly lower leptin and blood glucose levels and improved time trial performance over 20 km, which corresponded with a higher muscle oxygen flux compared to placebo. Muscle AMPK Thr172 phosphorylation significantly increased after 60 min exercise following G. pentaphyllum supplementation. AMPK Thr172 phosphorylation levels relative to total AMPK increased earlier following exercise with G. pentaphyllum compared to placebo. Total ACC-α was lower following G. pentaphyllum supplementation compared to placebo. While further research is warranted, G. pentaphyllum supplementation improved exercise performance in healthy untrained males, which corresponded with improved mitochondrial respiration, altered AMPK and ACC, and decreased plasma leptin and glucose levels.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Leptina , Humanos , Masculino , Proteínas Quinasas Activadas por AMP/metabolismo , Estudios Cruzados , Gynostemma , Extractos Vegetales/farmacología
3.
Hum Reprod ; 37(5): 1018-1029, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35325125

RESUMEN

STUDY QUESTION: Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT. WHAT IS KNOWN ALREADY: Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT. STUDY DESIGN, SIZE, DURATION: This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% peak heart rate, N = 14) or HIIT (>90% peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic-hyperinsulinaemic clamp). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition. MAIN RESULTS AND THE ROLE OF CHANCE: Both HIIT and MICT improved VO2peak (HIIT; Δ 5.8 ± 2.6 ml/kg/min, P < 0.001 and MICT; Δ 3.2 ± 2 ml/kg/min, P < 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (ß = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (ß = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (ß = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study has a small sample size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication. WIDER IMPLICATIONS OF THE FINDINGS: Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: ACTRN12615000242527. TRIAL REGISTRATION DATE: 19 February 2015. DATE OF FIRST PATIENT'S ENROLMENT: 27 May 2016.


Asunto(s)
Entrenamiento de Intervalos de Alta Intensidad , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Adulto , Australia , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Humanos , Sobrepeso/complicaciones , Sobrepeso/terapia , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/terapia
4.
J Appl Physiol (1985) ; 127(5): 1403-1418, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31513450

RESUMEN

We determined the effects of cold water immersion (CWI) on long-term adaptations and post-exercise molecular responses in skeletal muscle before and after resistance training. Sixteen men (22.9 ± 4.6 y; 85.1 ± 17.9 kg; mean ± SD) performed resistance training (3 day/wk) for 7 wk, with each session followed by either CWI [15 min at 10°C, CWI (COLD) group, n = 8] or passive recovery (15 min at 23°C, control group, n = 8). Exercise performance [one-repetition maximum (1-RM) leg press and bench press, countermovement jump, squat jump, and ballistic push-up], body composition (dual X-ray absorptiometry), and post-exercise (i.e., +1 and +48 h) molecular responses were assessed before and after training. Improvements in 1-RM leg press were similar between groups [130 ± 69 kg, pooled effect size (ES): 1.53 ± 90% confidence interval (CI) 0.49], whereas increases in type II muscle fiber cross-sectional area were attenuated with CWI (-1,959 ± 1,675 µM2 ; ES: -1.37 ± 0.99). Post-exercise mechanistic target of rapamycin complex 1 signaling (rps6 phosphorylation) was blunted for COLD at post-training (POST) +1 h (-0.4-fold, ES: -0.69 ± 0.86) and POST +48 h (-0.2-fold, ES: -1.33 ± 0.82), whereas basal protein degradation markers (FOX-O1 protein content) were increased (1.3-fold, ES: 2.17 ± 2.22). Training-induced increases in heat shock protein (HSP) 27 protein content were attenuated for COLD (-0.8-fold, ES: -0.94 ± 0.82), which also reduced total HSP72 protein content (-0.7-fold, ES: -0.79 ± 0.57). CWI blunted resistance training-induced muscle fiber hypertrophy, but not maximal strength, potentially via reduced skeletal muscle protein anabolism and increased catabolism. Post-exercise CWI should therefore be avoided if muscle hypertrophy is desired.NEW & NOTEWORTHY This study adds to existing evidence that post-exercise cold water immersion attenuates muscle fiber growth with resistance training, which is potentially mediated by attenuated post-exercise increases in markers of skeletal muscle anabolism coupled with increased catabolism and suggests that blunted muscle fiber growth with cold water immersion does not necessarily translate to impaired strength development.


Asunto(s)
Frío , Inmersión , Fibras Musculares Esqueléticas/fisiología , Fuerza Muscular/fisiología , Recuperación de la Función/fisiología , Entrenamiento de Fuerza/métodos , Adolescente , Adulto , Proteínas de Choque Térmico/metabolismo , Humanos , Hipertrofia , Masculino , Fibras Musculares Esqueléticas/patología , Adulto Joven
5.
Sci Rep ; 8(1): 560, 2018 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-29330460

RESUMEN

Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and ribosome biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in ribosome biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alone.


Asunto(s)
Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Músculo Esquelético/metabolismo , Acondicionamiento Físico Humano/métodos , Ribosomas/metabolismo , Entrenamiento de Intervalos de Alta Intensidad/métodos , Humanos , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , ARN Ribosómico/genética , ARN Ribosómico 28S/genética , ARN Ribosómico 5.8S/genética , Entrenamiento de Fuerza/métodos , Ribosomas/genética , Transducción de Señal
6.
J Appl Physiol (1985) ; 120(4): 391-8, 2016 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-26635348

RESUMEN

Beetroot juice, which is rich in nitrate (NO3 (-)), has been shown in some studies to decrease oxygen consumption (V̇o2) for a given exercise workload, i.e., increasing efficiency and exercise tolerance. Few studies have examined the effect of beetroot juice or nitrate supplementation on exercise metabolism. Eight healthy recreationally active males participated in three trials involving ingestion of either beetroot juice (Beet; ∼8 mmol NO3 (-)), Placebo (nitrate-depleted Beet), or Beet + mouthwash (Beet+MW), all of which were performed in a randomized single-blind crossover design. Two-and-a-half hours later, participants cycled for 60 min on an ergometer at 65% of V̇o2 peak. [6,6-(2)H]glucose was infused to determine glucose kinetics, blood samples obtained throughout exercise, and skeletal muscle biopsies that were obtained pre- and postexercise. Plasma nitrite [NO2 (-)] increased significantly (∼130%) with Beet, and this was attenuated in MW+Beet. Beet and Beet+MW had no significant effect on oxygen consumption, blood glucose, blood lactate, plasma nonesterified fatty acids, or plasma insulin during exercise. Beet and Beet+MW also had no significant effect on the increase in glucose disposal during exercise. In addition, Beet and Beet+MW had no significant effect on the decrease in muscle glycogen and phosphocreatine and the increase in muscle creatine, lactate, and phosphorylated acetyl CoA carboxylase during exercise. In conclusion, at the dose used, acute ingestion of beetroot juice had little effect on skeletal muscle metabolism during exercise.


Asunto(s)
Beta vulgaris , Ejercicio Físico/fisiología , Jugos de Frutas y Vegetales , Glucosa/metabolismo , Músculo Esquelético/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Sustancias para Mejorar el Rendimiento/farmacología , Acetil-CoA Carboxilasa/metabolismo , Adulto , Creatina/metabolismo , Estudios Cruzados , Suplementos Dietéticos , Ingestión de Alimentos/fisiología , Tolerancia al Ejercicio/efectos de los fármacos , Glucógeno/metabolismo , Humanos , Insulina/sangre , Cinética , Ácido Láctico/metabolismo , Masculino , Nitratos/metabolismo , Nitritos/metabolismo , Fosfocreatina/metabolismo , Resistencia Física/efectos de los fármacos , Método Simple Ciego
7.
Physiol Rep ; 3(2)2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25677549

RESUMEN

While training upregulates skeletal muscle Na(+), K(+)-ATPase (NKA), the effects of knee injury and associated disuse on muscle NKA remain unknown. This was therefore investigated in six healthy young adults with a torn anterior cruciate ligament, (KI; four females, two males; age 25.0 ± 4.9 years; injury duration 15 ± 17 weeks; mean ± SD) and seven age- and BMI-matched asymptomatic controls (CON; five females, two males). Each participant underwent a vastus lateralis muscle biopsy, on both legs in KI and one leg in CON. Muscle was analyzed for muscle fiber type and cross-sectional area (CSA), NKA content ([(3)H]ouabain binding), and α1-3 and ß1-2 isoform abundance. Participants also completed physical activity and knee function questionnaires (KI only); and underwent quadriceps peak isometric strength, thigh CSA and postural sway assessments in both injured and noninjured legs. NKA content was 20.1% lower in the knee-injured leg than the noninjured leg and 22.5% lower than CON. NKA α2 abundance was 63.0% lower in the knee-injured leg than the noninjured leg, with no differences in other NKA isoforms. Isometric strength and thigh CSA were 21.7% and 7.1% lower in the injured leg than the noninjured leg, respectively. In KI, postural sway did not differ between legs, but for two-legged standing was 43% higher than CON. Hence, muscle NKA content and α2 abundance were reduced in severe knee injury, which may contribute to impaired muscle function. Restoration of muscle NKA may be important in rehabilitation of muscle function after knee and other lower limb injury.

8.
Brain Behav Immun ; 39: 80-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24434040

RESUMEN

Aging is associated with increased circulating pro-inflammatory and lower anti-inflammatory cytokines. Exercise training, in addition to improving muscle function, reduces these circulating pro-inflammatory cytokines. Yet, few studies have evaluated changes in the expression of cytokines within skeletal muscle after exercise training. The aim of the current study was to examine the expression of cytokines both at rest and following a bout of isokinetic exercise performed before and after 12weeks of resistance exercise training in young (n=8, 20.3±0.8yr) and elderly men (n=8, 66.9±1.6yr). Protein expression of various cytokines was determined in muscle homogenates. The expression of MCP-1, IL-8 and IL-6 (which are traditionally classified as 'pro-inflammatory') increased substantially after acute exercise. By contrast, the expression of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 increased only slightly (or not at all) after acute exercise. These responses were not significantly different between young and elderly men, either before or after 12weeks of exercise training. However, compared with the young men, the expression of pro-inflammatory cytokines 2h post exercise tended to be greater in the elderly men prior to training. Training attenuated this difference. These data suggest that the inflammatory response to unaccustomed exercise increases with age. Furthermore, regular exercise training may help to normalize this inflammatory response, which could have important implications for muscle regeneration and adaptation in the elderly.


Asunto(s)
Citocinas/metabolismo , Ejercicio Físico/fisiología , Músculo Esquelético/metabolismo , Adolescente , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
11.
Muscle Nerve ; 46(3): 407-12, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22907232

RESUMEN

INTRODUCTION AND METHODS: This study compared changes in myokine and myogenic genes following resistance exercise (3 sets of 12 repetitions of maximal unilateral knee extension) in 20 elderly men (67.8 ± 1.0 years) and 15 elderly women (67.2 ± 1.5 years). RESULTS: Monocyte chemotactic protein (MCP)-1, macrophage inhibitory protein (MIP)-1ß, interleukin (IL)-6 and MyoD mRNA increased significantly (P < 0.05), whereas myogenin and myostatin mRNA decreased significantly after exercise in both groups. Macrophage-1 (Mac-1) and MCP-3 mRNA did not change significantly after exercise in either group. MIP-1ß, Mac-1 and myostatin mRNA were significantly higher before and after exercise in men compared with women. In contrast, MCP-3 and myogenin mRNA were significantly higher before and after exercise in the women compared with the men. CONCLUSIONS: In elderly individuals, gender influences the mRNA expression of certain myokines and growth factors, both at rest and after resistance exercise. These differences may influence muscle regeneration following muscle injury.


Asunto(s)
Ejercicio Físico/fisiología , Inflamación/metabolismo , Músculo Esquelético/metabolismo , Entrenamiento de Fuerza , Anciano , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL4/genética , Quimiocina CCL4/metabolismo , Quimiocina CCL7/genética , Quimiocina CCL7/metabolismo , Femenino , Expresión Génica , Humanos , Inflamación/fisiopatología , Interleucina-6/genética , Interleucina-6/metabolismo , Antígeno de Macrófago-1/genética , Antígeno de Macrófago-1/metabolismo , Masculino , Persona de Mediana Edad , Desarrollo de Músculos , Músculo Esquelético/fisiopatología , Miogenina/genética , Miogenina/metabolismo , Factores Sexuales
12.
J Appl Physiol (1985) ; 113(2): 206-14, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22628371

RESUMEN

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (Vo(2peak)) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of l-[ring-(13)C(6)] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups (P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs (P < 0.05). mTOR(Ser2448) phosphorylation in placebo increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ~4-fold in LOW (P < 0.01) and ~11 fold in NORM with nutrient (P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.


Asunto(s)
Anabolizantes/metabolismo , Tolerancia al Ejercicio/fisiología , Glucógeno/metabolismo , Insulina/sangre , Músculo Esquelético/fisiología , Consumo de Oxígeno/fisiología , Entrenamiento de Fuerza/métodos , Humanos , Masculino , Valores de Referencia , Adulto Joven
13.
Med Sci Sports Exerc ; 44(10): 1968-77, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22617396

RESUMEN

PURPOSE: We have previously shown that the aminoacidemia caused by the consumption of a rapidly digested protein after resistance exercise enhances muscle protein synthesis (MPS) more than the amino acid (AA) profile associated with a slowly digested protein. Here, we investigated whether differential feeding patterns of a whey protein mixture commencing before exercise affect postexercise intracellular signaling and MPS. METHODS: Twelve resistance-trained males performed leg resistance exercise 45 min after commencing each of three volume-matched nutrition protocols: placebo (PLAC, artificially sweetened water), BOLUS (25 g of whey protein + 5 g of leucine dissolved in artificially sweetened water; 1 × 500 mL), or PULSE (15 × 33-mL aliquots of BOLUS drink every 15 min). RESULTS: The preexercise rise in plasma AA concentration with PULSE was attenuated compared with BOLUS (P < 0.05); this effect was reversed after exercise, with two-fold greater leucine concentrations in PULSE compared with BOLUS (P < 0.05). One-hour postexercise, phosphorylation of p70 S6K(thr389) and rpS6(ser235/6) was increased above baseline with BOLUS and PULSE, but not PLAC (P < 0.05); furthermore, PULSE > BOLUS (P < 0.05). MPS throughout 5 h of recovery was higher with protein ingestion compared with PLAC (0.037 ± 0.007), with no differences between BOLUS or PULSE (0.085 ± 0.013 vs. 0.095 ± 0.010%.h(-1), respectively, P = 0.56). CONCLUSIONS: Manipulation of aminoacidemia before resistance exercise via different patterns of intake of protein altered plasma AA profiles and postexercise intracellular signaling. However, there was no difference in the enhancement of the muscle protein synthetic response after exercise. Protein sources producing a slow AA release, when consumed before resistance exercise in sufficient amounts, are as effective as rapidly digested proteins in promoting postexercise MPS.


Asunto(s)
Acidosis/sangre , Aminoácidos/sangre , Proteínas de la Leche/administración & dosificación , Proteínas Musculares/biosíntesis , Músculo Esquelético/metabolismo , Entrenamiento de Fuerza , Adulto , Humanos , Pierna/fisiología , Leucina/administración & dosificación , Masculino , Fosforilación , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina/metabolismo , Edulcorantes/administración & dosificación , Treonina/metabolismo , Proteína de Suero de Leche
14.
Med Sci Sports Exerc ; 43(9): 1626-34, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21311355

RESUMEN

PURPOSE: We have previously shown that local infusion of a nitric oxide synthase (NOS) inhibitor attenuates increases in leg glucose uptake during exercise in humans. We have also shown that infusion of the NOS substrate, l-arginine (l-Arg), increases glucose clearance, although the mechanisms involved were not determined. A potential mechanism for NO-mediated glucose disposal is via interactions with NOS and the energy sensor AMP-activated protein kinase (AMPK). The aim of this study was to determine the mechanism(s) by which l-Arg infusion increases glucose disposal during exercise in humans by examining total NOS activity and AMPK signaling. METHODS: Seven males cycled for 120 min at 64% ± 1% VO(2)peak, during which the [6,6-H]glucose tracer was infused. During the final 60 min of exercise, either saline alone (Control, CON), or saline containing l-Arg HCl (l-Arg, 30 g at 0.5 g·min(-1)) was coinfused in a double-blind, randomized, counterbalanced order. RESULTS: l-Arg increased the glucose rate of disappearance and glucose clearance rate during exercise; however, this was accompanied by a 150% increase in plasma insulin concentration from 65 to 75 min (P < 0.05) that remained significantly elevated until 90 min of exercise. Skeletal muscle AMPK signaling, nNOSµ phosphorylation by AMPK, and total NOS activity increased to a similar extent in the two trials. CONCLUSIONS: The increase in glucose disposal after l-Arg infusion during exercise is likely due to the significantly higher plasma insulin concentration.


Asunto(s)
Arginina/administración & dosificación , Ejercicio Físico/fisiología , Glucosa/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Adulto , Prueba de Esfuerzo , Humanos , Infusiones Intravenosas , Insulina/sangre , Masculino , Óxido Nítrico Sintasa de Tipo I/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Adulto Joven
15.
Muscle Nerve ; 43(3): 385-92, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21321954

RESUMEN

The JAK/STAT signaling pathway is essential for myogenic regeneration and is regulated by a diverse range of ligands, including interleukin-6 (IL-6) and platelet-derived growth factor-BB (PDGF-BB). Our aim was to evaluate the responsiveness of IL-6 and PDGF-BB to intense exercise, along with STAT3 activation, before and after 12 weeks of resistance training. In young men, IL-6 and PDGF-BB protein concentrations were quantified in biopsied muscle and increased at 3 h post-exercise (17.5-fold and 3-fold, respectively). The response was unaltered by 12 weeks of training. Similarly, STAT3 phosphorylation was elevated post-exercise (12.5-fold), irrespective of training status, as was the expression of downstream targets c-MYC (8-fold), c-FOS (4.5-fold), and SOCS3 (2.3-fold). Thus, intense exercise transiently increases IL-6 and PDGF-BB proteins, and STAT3 phosphorylation is increased. These responses are preserved after intense exercise. This suggests they are not modified by training and may be an essential component of the adaptive responses to intense exercise.


Asunto(s)
Ejercicio Físico/fisiología , Interleucina-6/biosíntesis , Quinasas Janus/sangre , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Entrenamiento de Fuerza , Factor de Transcripción STAT3/biosíntesis , Becaplermina , Humanos , Interleucina-6/sangre , Quinasas Janus/fisiología , Masculino , Fuerza Muscular/fisiología , Fosforilación/fisiología , Proteínas Proto-Oncogénicas c-sis , Entrenamiento de Fuerza/métodos , Factor de Transcripción STAT3/sangre , Transducción de Señal/fisiología , Factores de Tiempo , Adulto Joven
16.
Eur J Appl Physiol ; 111(7): 1473-83, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21165642

RESUMEN

The effect of nutrient availability on the acute molecular responses following repeated sprint exercise is unknown. The aim of this study was to determine skeletal muscle cellular and protein synthetic responses following repeated sprint exercise with nutrient provision. Eight healthy young male subjects undertook two sprint cycling sessions (10 × 6 s, 0.75 N m torque kg(-1), 54 s recovery) with either pre-exercise nutrient (24 g whey, 4.8 g leucine, 50 g maltodextrin) or non-caloric placebo ingestion. Muscle biopsies were taken from vastus lateralis at rest, and after 15 and 240 min post-exercise recovery to determine muscle cell signalling responses and protein synthesis by primed constant infusion of L: -[ring-(13)C(6)] phenylalanine. Peak and mean power outputs were similar between nutrient and placebo trials. Post-exercise myofibrillar protein synthetic rate was greater with nutrient ingestion compared with placebo (~48%, P < 0.05) but the rate of mitochondrial protein synthesis was similar between treatments. The increased myofibrillar protein synthesis following sprints with nutrient ingestion was associated with coordinated increases in Akt-mTOR-S6K-rpS6 phosphorylation 15 min post-exercise (~200-600%, P < 0.05), while there was no effect on these signalling molecules when exercise was undertaken in the fasted state. For the first time we report a beneficial effect of nutrient provision on anabolic signalling and muscle myofibrillar protein synthesis following repeated sprint exercise. Ingestion of protein/carbohydrate in close proximity to high-intensity sprint exercise provides an environment that increases cell signalling and protein synthesis.


Asunto(s)
Ingestión de Alimentos/fisiología , Músculo Esquelético/fisiología , Biosíntesis de Proteínas/fisiología , Carrera/fisiología , Aceleración , Adulto , Estudios Cruzados , Método Doble Ciego , Alimentos , Humanos , Masculino , Músculo Esquelético/metabolismo , Periodicidad , Placebos , Transducción de Señal/fisiología , Regulación hacia Arriba , Adulto Joven
17.
J Physiol ; 588(Pt 9): 1623-34, 2010 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-20308250

RESUMEN

There is evidence that reactive oxygen species (ROS) signalling is required for normal increases in glucose uptake during contraction of isolated mouse skeletal muscle, and that AMP-activated protein kinase (AMPK) is involved. The aim of this study was to determine whether ROS signalling is involved in the regulation of glucose disposal and AMPK activation during moderate-intensity exercise in humans. Nine healthy males completed 80 min of cycle ergometry at 62 +/- 1% of peak oxygen consumption ( V(O(2)peak).A 6,6-(2)H-glucose tracer was infused at rest and during exercise, and in a double-blind randomised cross-over design, N-acetylcysteine (NAC) or saline (CON) was co-infused. NAC was infused at 125 mg kg(1) h(1) for 15 min and then at 25 mg kg(1) h(1) for 20 min before and throughout exercise. NAC infusion elevated plasma NAC and cysteine, and muscle NAC and cysteine concentrations during exercise. Although neither NAC infusion nor exercise significantly affected muscle reduced or oxidised glutathione (GSH or GSSG) concentration (P > 0.05), S-glutathionylation (an indicator of oxidative stress) of a protein band of approximately 270 kDa was increased approximately 3-fold with contraction and this increase was prevented by NAC infusion. Despite this, exercised-induced increases in tracer determined glucose disposal, plasma lactate, plasma non-esterified fatty acids (NEFAs), and decreases in plasma insulin were not affected by NAC infusion. In addition, skeletal muscle AMPKalpha and acetyl-CoA carboxylase-beta (ACCbeta) phosphorylation increased during exercise by approximately 3- and approximately 6-fold (P < 0.05), respectively, and this was not affected by NAC infusion. Unlike findings in mouse muscle ex vivo, NAC does not attenuate skeletal muscle glucose disposal or AMPK activation during moderate-intensity exercise in humans.


Asunto(s)
Acetilcisteína/farmacología , Ejercicio Físico/fisiología , Depuradores de Radicales Libres/farmacología , Glucosa/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Acetilcisteína/administración & dosificación , Acetilcisteína/metabolismo , Adulto , Umbral Anaerobio/efectos de los fármacos , Umbral Anaerobio/fisiología , Estudios Cruzados , Cisteína/sangre , Cistina/sangre , Método Doble Ciego , Prueba de Esfuerzo , Ácidos Grasos no Esterificados/metabolismo , Depuradores de Radicales Libres/administración & dosificación , Glutatión/biosíntesis , Frecuencia Cardíaca/fisiología , Humanos , Infusiones Intravenosas , Ácido Láctico/sangre , Masculino , Músculo Esquelético/metabolismo , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Adulto Joven
18.
Exp Physiol ; 95(2): 351-8, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19854796

RESUMEN

We have previously demonstrated that well-trained subjects who completed a 3 week training programme in which selected high-intensity interval training (HIT) sessions were commenced with low muscle glycogen content increased the maximal activities of several oxidative enzymes that promote endurance adaptations to a greater extent than subjects who began all training sessions with normal glycogen levels. The aim of the present study was to investigate acute skeletal muscle signalling responses to a single bout of HIT commenced with low or normal muscle glycogen stores in an attempt to elucidate potential mechanism(s) that might underlie our previous observations. Six endurance-trained cyclists/triathletes performed a 100 min ride at approximately 70% peak O(2) uptake (AT) on day 1 and HIT (8 x 5 min work bouts at maximal self-selected effort with 1 min rest) 24 h later (HIGH). Another six subjects, matched for fitness and training history, performed AT on day 1 then 1-2 h later, HIT (LOW). Muscle biopsies were taken before and after HIT. Muscle glycogen concentration was higher in HIGH versus LOW before the HIT (390 +/- 28 versus 256 +/- 67 micromol (g dry wt)(1)). After HIT, glycogen levels were reduced in both groups (P < 0.05) but HIGH was elevated compared with LOW (229 +/- 29 versus 124 +/- 41 micromol (g dry wt)(1); P < 0.05). Phosphorylation of 5 AMP-activated protein kinase (AMPK) increased after HIT, but the magnitude of increase was greater in LOW (P < 0.05). Despite the augmented AMPK response in LOW after HIT, selected downstream AMPK substrates were similar between groups. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was unchanged for both groups before and after the HIT training sessions. We conclude that despite a greater activation AMPK phosphorylation when HIT was commenced with low compared with normal muscle glycogen availability, the localization and phosphorylation state of selected downstream targets of AMPK were similar in response to the two interventions.


Asunto(s)
Glucógeno/metabolismo , Músculo Esquelético/fisiología , Resistencia Física/fisiología , Esfuerzo Físico/fisiología , Aptitud Física/fisiología , Transducción de Señal/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Humanos , Masculino , Adulto Joven
19.
J Physiol ; 587(Pt 24): 5951-8, 2009 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-19884317

RESUMEN

Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP-activated protein kinase (AMPK) and the calcium-calmodulin-dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation-dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise.


Asunto(s)
Adaptación Fisiológica/fisiología , Ejercicio Físico/fisiología , Histonas/metabolismo , Contracción Muscular/fisiología , Esfuerzo Físico/fisiología , Humanos , Masculino , Músculo Esquelético/fisiología , Adulto Joven
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