RESUMO
Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, little is known about the mechanisms responsible for these negative traits. With the complexities surrounding these unknowns and the lack of progress to date in development of effective interventions, there is a need for alternative approaches. Metabolomics is the study of the full array of metabolites within cells or tissues, which collectively constitute the metabolome. As metabolomics allows for the assessment of the cellular metabolic state in response to physiological stimuli, any chronic change in the metabolome is likely to reflect adaptation in the physiological phenotype of an organism. This, therefore, provides a holistic and unbiased approach that could be applied to potentially uncover important novel facets in the pathophysiology of muscle decline in ageing and disease, as well as identifying prognostic markers of those at risk of decline. This review will aim to highlight the current knowledge and potential impact of metabolomics in the study of muscle mass loss and deconditioning in humans and will highlight key areas for future research.
Assuntos
Envelhecimento , Metaboloma , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Aminoácidos/metabolismo , Animais , Caquexia/metabolismo , Caquexia/fisiopatologia , Metabolismo Energético , Humanos , Metabolismo dos Lipídeos , Metabolômica , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologiaRESUMO
BACKGROUND: Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of patients with mild to inactive disease. Fatigue is the commonest reason for work absence in IBD, and patients often report fatigue burden to be greater than that of primary disease symptoms. Relatively few evidence-based treatment options exist, and the aetiology is poorly understood. AIM: To review the available data and suggest a possible aetiology of IBD fatigue and to consider the efficacy of existing management strategies and highlight potential future interventions. METHODS: We reviewed fatigue-related literature in IBD using PubMed database. RESULTS: Disease related factors such as inflammation and pharmacological treatments negatively impact skeletal muscle and brain physiology, likely contributing to fatigue symptoms. Secondary factors such as malnutrition, anaemia, sleep disturbance and psychological comorbidity are potential determinants. Immune profile, faecal microbiota composition and physical fitness differ significantly between fatigued and non-fatigued patients, suggesting these may be aetiological factors. Solution-focused therapy, high-dosage thiamine supplementation and biological therapy may reduce fatigue perception in IBD. The effect of physical activity interventions is inconclusive. CONCLUSIONS: A multimodal approach is likely required to treat IBD fatigue. Established reversible factors like anaemia, micronutrient deficiencies and active disease should initially be resolved. Psychosocial intervention shows potential efficacy in reducing fatigue perception in quiescent disease. Restoring physical deconditioning by exercise training intervention may further improve fatigue burden.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Exercício Físico , Fadiga/epidemiologia , Fadiga/etiologia , Fadiga/terapia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/terapia , Aptidão Física , Qualidade de VidaRESUMO
Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2 ) performed 1 h of cycling at 50% VO2 max and, on a separate occasion, underwent a 60 mU/m2 /min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L-carnitine L-tartrate (n = 7). During supplementation, participants performed twice-weekly cycling for 1 h at 50% VO2 max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2 max. L-carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin-stimulated whole-body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine-mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.
Assuntos
Carnitina/metabolismo , Exercício Físico , Gorduras/metabolismo , Músculo Esquelético/metabolismo , Idoso , Humanos , Masculino , OxirreduçãoRESUMO
BACKGROUND & AIMS: Malnutrition has been recognized as a major risk factor for adverse postoperative outcomes. The ESPEN Symposium on perioperative nutrition was held in Nottingham, UK, on 14-15 October 2018 and the aims of this document were to highlight the scientific basis for the nutritional and metabolic management of surgical patients. METHODS: This paper represents the opinion of experts in this multidisciplinary field and those of a patient and caregiver, based on current evidence. It highlights the current state of the art. RESULTS: Surgical patients may present with varying degrees of malnutrition, sarcopenia, cachexia, obesity and myosteatosis. Preoperative optimization can help improve outcomes. Perioperative fluid therapy should aim at keeping the patient in as near zero fluid and electrolyte balance as possible. Similarly, glycemic control is especially important in those patients with poorly controlled diabetes, with a stepwise increase in the risk of infectious complications and mortality per increasing HbA1c. Immobilization can induce a decline in basal energy expenditure, reduced insulin sensitivity, anabolic resistance to protein nutrition and muscle strength, all of which impair clinical outcomes. There is a role for pharmaconutrition, pre-, pro- and syn-biotics, with the evidence being stronger in those undergoing surgery for gastrointestinal cancer. CONCLUSIONS: Nutritional assessment of the surgical patient together with the appropriate interventions to restore the energy deficit, avoid weight loss, preserve the gut microbiome and improve functional performance are all necessary components of the nutritional, metabolic and functional conditioning of the surgical patient.
Assuntos
Hidratação/métodos , Desnutrição/prevenção & controle , Terapia Nutricional/métodos , Assistência Perioperatória/métodos , Desequilíbrio Hidroeletrolítico/prevenção & controle , Congressos como Assunto , Europa (Continente) , Hidratação/normas , Humanos , Desnutrição/etiologia , Terapia Nutricional/normas , Assistência Perioperatória/normas , Guias de Prática Clínica como Assunto , Sociedades Médicas , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Desequilíbrio Hidroeletrolítico/etiologiaRESUMO
Background: Voluntary resistance exercise (RE) training increases muscle mass and strength in patients with chronic obstructive pulmonary disease (COPD). Nonvolitional transcutaneous neuromuscular electrical stimulation (NMES) may be an alternative strategy for reducing ambulatory muscle weakness in patients unable to perform RE training, but little comparative data are available. This study, therefore, investigated changes in muscle mRNA abundance of a number of gene targets in response to a single bout of NMES compared with RE. Methods: Twenty-six patients with stable COPD (15 male; FEV1, 43±18% predicted; age, 64±8 years; fat free mass index, 16.6±1.8 kg/m2) undertook 30 minutes of quadriceps NMES (50 Hz, current at the limit of tolerance) or 5×30 maximal voluntary isokinetic knee extensions. Vastus lateralis muscle biopsies were obtained at rest immediately before and 24 hours after intervention. Expression of 384 targeted mRNA transcripts was assessed by real time TaqMan PCR. Significant change in expression from baseline was determined using the ΔΔCT method with a false discovery rate (FDR) of <5%. Results: NMES and RE altered mRNA abundance of 18 and 68 genes, respectively (FDR <5%), of which 14 genes were common to both interventions and of the same magnitude of fold change. Biological functions of upregulated genes included inflammation, hypertrophy, muscle protein turnover, and muscle growth, whilst downregulated genes included mitochondrial and cell signaling functions. Conclusions: Compared with NMES, RE had a broader impact on mRNA abundance and, therefore, appears to be the superior intervention for maximizing transcriptional responses in the quadriceps of patients with COPD. However, if voluntary RE is not feasible in a clinical setting, NMES by modifying expression of genes known to impact upon muscle mass and strength may have a positive influence on muscle function.
Assuntos
Contração Muscular , Músculo Esquelético/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , RNA Mensageiro/metabolismo , Treinamento Resistido , Estimulação Elétrica Nervosa Transcutânea , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Músculo Esquelético/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , RNA Mensageiro/genética , Fatores de Tempo , Ativação Transcricional , Resultado do TratamentoRESUMO
Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m2 ) performed 2 × 3 minute bouts of cycling exercise at 100% Wattmax , separated by 5 minutes of rest. Fourteen volunteers repeated this protocol following 24 weeks of HIIT and twice-daily consumption of 80 g carbohydrate (CON) or 3 g l-carnitine+carbohydrate (CARN). Before HIIT, muscle phosphocreatine (PCr) degradation (P<.0001), glycogenolysis (P<.0005), PDC activation (P<.05), and acetylcarnitine (P<.005) were 2.3-, 2.1-, 1.5-, and 1.5-fold greater, respectively, in exercise bout two compared to bout 1, while lactate accumulation tended (P<.07) to be 1.5-fold greater. Following HIIT, muscle free carnitine was 30% greater in CARN vs CON at rest and remained 40% elevated prior to the start of bout 2 (P<.05). Following bout 2, free carnitine content, PCr degradation, glycogenolysis, lactate accumulation, and PDC activation were all similar between CON and CARN, albeit markedly lower than before HIIT. VO2max , Wattmax , and work output were similarly increased in CON and CARN, by 9, 15, and 23% (P<.001). In summary, increased reliance on non-mitochondrial ATP resynthesis during a second bout of intense exercise is accompanied by increased carnitine acetylation. Augmenting muscle carnitine during 24 weeks of HIIT did not alter this, nor did it enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone.
Assuntos
Adaptação Fisiológica , Carnitina/administração & dosagem , Treinamento Intervalado de Alta Intensidade , Músculo Esquelético/metabolismo , Acetilação , Trifosfato de Adenosina/metabolismo , Adulto , Carnitina/metabolismo , Carboidratos da Dieta/administração & dosagem , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Ácido Láctico , Masculino , Adulto JovemRESUMO
BACKGROUND & AIMS: Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP). METHODS: Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13C6-phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting. RESULTS: Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0-2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0-4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05). CONCLUSIONS: In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism.
Assuntos
Exercício Físico/fisiologia , Leucina , Músculo Esquelético/efeitos dos fármacos , Proteínas do Soro do Leite , Idoso , Aminoácidos Essenciais/sangue , Suplementos Nutricionais , Feminino , Humanos , Insulina/sangue , Perna (Membro)/irrigação sanguínea , Perna (Membro)/fisiologia , Leucina/administração & dosagem , Leucina/farmacologia , Pessoa de Meia-Idade , Proteínas Musculares/metabolismo , Proteínas do Soro do Leite/administração & dosagem , Proteínas do Soro do Leite/farmacologiaRESUMO
KEY POINTS: Meldonium inhibits endogenous carnitine synthesis and tissue uptake, and accelerates urinary carnitine excretion, although the impact of meldonium-mediated muscle carnitine depletion on whole-body fuel selection, and muscle fuel metabolism and its molecular regulation is under-investigated. Ten days of oral meldonium administration did not impact on food or fluid intake, physical activity levels or body weight gain in the rat, whereas it depleted muscle carnitine content (all moieties), increased whole-body carbohydrate oxidation and muscle and liver glycogen utilization, and reduced whole-body fat oxidation. Meldonium reduced carnitine transporter protein expression across muscles of different contractile and metabolic phenotypes. A TaqMan PCR low-density array card approach revealed the abundance of 189 mRNAs regulating fuel selection was altered in soleus muscle by meldonium, highlighting the modulation of discrete cellular functions and metabolic pathways. These novel findings strongly support the premise that muscle carnitine availability is a primary regulator of fuel selection in vivo. ABSTRACT: The body carnitine pool is primarily confined to skeletal muscle, where it regulates carbohydrate (CHO) and fat usage. Meldonium (3-(2,2,2-trimethylhydrazinium)-propionate) inhibits carnitine synthesis and tissue uptake, although the impact of carnitine depletion on whole-body fuel selection, muscle fuel metabolism and its molecular regulation is under-investigated. Male lean Zucker rats received water (control, n = 8) or meldonium-supplemented water (meldonium, n = 8) for 10 days [1.6 g kg-1 body mass (BM) day-1 days 1-2, 0.8 g kg-1 BM day-1 thereafter]. From days 7-10, animals were housed in indirect calorimetry chambers after which soleus muscle and liver were harvested. Food and fluid intake, weight gain and physical activity levels were similar between groups from days 7 to 10. Compared to control, meldonium depleted muscle total carnitine (P < 0.001) and all carnitine esters. Furthermore, whole-body fat oxidation was less (P < 0.001) and CHO oxidation was greater (P < 0.05) compared to the control, whereas soleus and liver glycogen contents were less (P < 0.01 and P < 0.01, respectively). In a second study, male Wistar rats received water (n = 8) or meldonium-supplemented water (n = 8) as above, and kidney, heart and extensor digitorum longus muscle (EDL) and soleus muscles were collected. Compared to control, meldonium depleted total carnitine content (all P < 0.001), reduced carnitine transporter protein and glycogen content, and increased pyruvate dehydrogenase kinase 4 mRNA abundance in the heart, EDL and soleus. In total, 189 mRNAs regulating fuel selection were differentially expressed in soleus in meldonium vs. control, and a number of cellular functions and pathways strongly associated with carnitine depletion were identified. Collectively, these data firmly support the premise that muscle carnitine availability is a primary regulator of fuel selection in vivo.
Assuntos
Carnitina/metabolismo , Metilidrazinas/farmacologia , Músculo Esquelético/efeitos dos fármacos , Animais , Metabolismo Energético/efeitos dos fármacos , Glicogênio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , RNA Mensageiro/metabolismo , Ratos Wistar , Ratos Zucker , Membro 5 da Família 22 de Carreadores de Soluto/metabolismoRESUMO
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5 ± 0.1 mg·kg-1·day-1) for 2 weeks before and during 24 h continuous intravenous infusion of LPS (15 µg·kg-1·h-1) or saline. Rosi blunted LPS-induced increases in muscle tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% (P<0.05) and 64% (P<0.01) respectively. Furthermore, Rosi suppressed the LPS-induced reduction in phosphorylated AKT and phosphorylated Forkhead box O (FOXO) 1 protein, as well as the up-regulation of muscle RING finger 1 (MuRF1; P<0.01) mRNA and the LPS-induced increase in 20S proteasome activity (P<0.05). Accordingly, LPS reduced the muscle protein:DNA ratio (â¼30%, P<0.001), which Rosi offset. Increased muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA (P<0.001) and muscle lactate accumulation (P<0.001) during endotoxaemia were suppressed by Rosi. Thus, pre-treatment with Rosi reduced muscle cytokine accumulation and blunted muscle protein loss and lactate accumulation during endotoxaemia, and at least in part by reducing activation of molecular events known to increase muscle protein breakdown and mitochondrial pyruvate use.
Assuntos
Endotoxemia/tratamento farmacológico , Ácido Láctico/metabolismo , Proteínas Musculares/metabolismo , PPAR gama/agonistas , Tiazolidinedionas/uso terapêutico , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Endotoxemia/genética , Endotoxemia/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Interleucina-6/biossíntese , Interleucina-6/genética , Masculino , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , RNA Mensageiro/genética , Ratos Sprague-Dawley , Rosiglitazona , Tiazolidinedionas/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
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 ± 2.5 yr; n = 8/group): bolus whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)]. Using [(13)C6]phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and in response to both feeding (FED) and feeding plus exercise (FED-EX; 6 × 8 knee extensions at 75% 1-repetition maximum). We also quantified plasma insulin/AA concentrations, whole leg (LBF)/muscle microvascular blood flow (MBF), and muscle anabolic signaling by phosphoimmunoblotting. 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, whereas 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 0-2 h (P < 0.05), abating thereafter (0-4 h, P > 0.05). In contrast, after FED-EX, MPS increased at 0-2 h and remained elevated at 0-4 h (P < 0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr(389) increased after FED-EX (2 h, 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.
Assuntos
Aminoácidos Essenciais/administração & dosagem , Proteínas Alimentares/administração & dosagem , Exercício Físico/fisiologia , Leucina/administração & dosagem , Proteínas do Leite/administração & dosagem , Proteínas Musculares/biossíntese , Músculo Esquelético/efeitos dos fármacos , Descanso/fisiologia , Idoso , Aminoácidos Essenciais/sangue , Dieta , Suplementos Nutricionais , Feminino , Humanos , Insulina/sangue , Leucina/sangue , Pessoa de Meia-Idade , Proteínas Musculares/efeitos dos fármacos , Músculo Esquelético/metabolismo , Proteínas do Soro do LeiteRESUMO
Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [(13)C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ~12 h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, aging, and disease while querying the utility of tracer techniques to predict the long-term efficacy of anabolic/anticatabolic 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 ± 3.5 yr) undertook one-legged resistance exercise over an 8-day period (4 × 8-10 repetitions, 80% 1RM every 2nd day, to yield "nonexercised" vs. "exercise" leg comparisons), with vastus lateralis biopsies taken bilaterally at 0, 2, 4, and 8 days. After day 0 biopsies, participants consumed a D2O bolus (150 ml, 70 atom%); saliva was collected daily. Fractional synthetic rates (FSRs) 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%/day. In the nonexercised leg, MyoPS was 1.45 ± 0.10, 1.47 ± 0.06, and 1.35 ± 0.07%/day at 0-2, 0-4, and 0-8 days, respectively (~0.05-0.06%/h). MyoPS was greater in the exercised leg (0-2 days: 1.97 ± 0.13%/day; 0-4 days: 1.96 ± 0.15%/day, P < 0.01; 0-8 days: 1.79 ± 0.12%/day, P < 0.05). CPS was slower than MyoPS but followed a similar pattern, with the exercised leg tending to yield greater FSRs (0-2 days: 1.14 ± 0.13 vs. 1.45 ± 0.15%/day; 0-4 days: 1.13 ± 0.07%/day vs. 1.47 ± 0.18%/day; 0-8 days: 1.03 ± 0.09%/day vs. 1.40 ± 0.11%/day). 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.
Assuntos
Óxido de Deutério/farmacologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Biossíntese de Proteínas/fisiologia , Adulto , Exercício Físico/fisiologia , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Miofibrilas/efeitos dos fármacos , Miofibrilas/metabolismo , Treinamento ResistidoRESUMO
Reduced skeletal muscle free coenzyme A (CoASH) availability may decrease the contribution of fat oxidation to ATP production during high-intensity, submaximal exercise or, alternatively, limit pyruvate dehydrogenase complex (PDC) flux and thereby carbohydrate oxidation. Here we attempted to increase the muscle CoASH pool in humans, via pantothenic acid and cysteine feeding, in order to elucidate the role of CoASH availability on muscle fuel metabolism during exercise. On three occasions, eight healthy male volunteers (age 22.9 ± 1.4 yr, body mass index 24.2 ± 1.5 kg/m(2)) cycled at 75% maximal oxygen uptake (Vo(2max)) to exhaustion, followed by a 15-min work output performance test. Muscle biopsies were obtained at rest, and after 60 min and 91.3 ± 3.1 min of exercise (time to exhaustion on baseline visit) on each occasion. Two weeks following the first visit (baseline), 1 wk of oral supplementation with either 3 g/day of a placebo control (glucose polymer; CON) or 1.5 g/day each of d-pantothenic acid and l-cysteine (CP) was carried out prior to the second and third visits in a randomized, counterbalanced, double-blind manner, leaving a 3-wk gap in total between each visit. Resting muscle CoASH content was not altered by supplementation in any visit. Following 60 min of exercise, muscle CoASH content was reduced by 13% from rest in all three visits (P < 0.05), and similar changes in the respiratory exchange ratio, glycogenolysis (â¼235 mmol/kg dry muscle), PCr degradation (â¼57 mmol/kg dry muscle), and lactate (â¼25 mmol/kg dry muscle) and acetylcarnitine (â¼12 mmol(.)kg/dry muscle) accumulation was observed during exercise when comparing visits. Furthermore, no difference in work output was observed when comparing CON and CP. Acute feeding with pantothenic acid and cysteine does not alter muscle CoASH content and consequently does not impact on muscle fuel metabolism or performance during exercise in humans.
Assuntos
Coenzima A/metabolismo , Cisteína/administração & dosagem , Tolerância ao Exercício/efeitos dos fármacos , Músculo Esquelético/enzimologia , Ácido Pantotênico/administração & dosagem , Biomarcadores/análise , Biomarcadores/metabolismo , Biópsia , Teste de Esforço , Tolerância ao Exercício/fisiologia , Glicogênio/análise , Glicogênio/metabolismo , Humanos , Masculino , Músculo Esquelético/química , Músculo Esquelético/efeitos dos fármacos , Consumo de Oxigênio , Adulto JovemRESUMO
We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50% , 30 min at 80% , then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50% , the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80% , muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an improvement in exercise performance.
Assuntos
Carnitina/administração & dosagem , Carnitina/metabolismo , Carboidratos da Dieta/administração & dosagem , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/metabolismo , Administração Oral , Adulto , Método Duplo-Cego , Teste de Esforço/métodos , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Esportes/fisiologia , Fatores de Tempo , Adulto JovemRESUMO
RATIONALE: Skeletal muscle strength and bulk are reduced in patients with chronic obstructive pulmonary disease (COPD) and influence quality of life, survival, and utilization of health care resources. Exercise training during pulmonary rehabilitation (PR) can reverse some of these effects. In athletes and healthy elderly individuals, dietary creatine supplementation (CrS) has been shown to augment high-intensity exercise training, thereby increasing muscle mass. OBJECTIVES: This article examines the effect of CrS on functional exercise capacity and muscle performance in people with COPD. METHODS: One hundred subjects with COPD (mean [SD] age, 68.2 [8.2] yr; FEV(1), 44.0 [19.6] %predicted) were randomized to a double-blind, placebo-controlled, parallel group trial of CrS during 7 weeks of PR encompassing aerobic and resistance exercises. Subjects ingested creatine (22 g/d loading for 5 d; maintenance, 3.76 g/d throughout PR) or placebo. Baseline, postloading, and postrehabilitation measurements included pulmonary function, body composition, peripheral muscle strength, and functional performance (shuttle walking tests). A volunteer subgroup (n = 44) had pre- and postloading quadriceps muscle biopsies. MEASUREMENTS AND MAIN RESULTS: Eighty subjects completed the trial (38 creatine, 42 placebo). All outcome measures significantly improved after PR. There were no significant differences between groups post-PR (mean [SD] change in incremental shuttle walk distance, 84 [79] m in the creatine group vs. 83.8 [60] m in the placebo group; P = 1.0; knee extensor work, 19.2 [16] Nm [Newton meters] in the creatine group vs. 19.5 [17] Nm in the placebo group; P = 0.9). Muscle biopsies showed evidence of creatine uptake. CONCLUSIONS: This adequately powered, randomized, placebo-controlled trial shows that CrS does not augment the substantial training effect of multidisciplinary PR for patients with COPD. Clinical trial registered with https://portal.nihr.ac.uk/Pages/NRRArchiveSearch.aspx (NO123138126).
Assuntos
Creatina , Suplementos Nutricionais , Terapia por Exercício/métodos , Tolerância ao Exercício , Doença Pulmonar Obstrutiva Crônica/reabilitação , Idoso , Exercício Físico/fisiologia , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Resultado do Tratamento , Capacidade VitalRESUMO
Due to the current lack of clarity, we examined whether 5 days of dietary creatine (Cr) supplementation per se can influence the glycogen content of human skeletal muscle. Six healthy male volunteers participated in the study, reporting to the laboratory on four occasions to exercise to the point of volitional exhaustion, each after 3 days of a controlled normal habitual dietary intake. After a familiarization visit, participants cycled to exhaustion in the absence of any supplementation (N), and then 2 wk later again they cycled to exhaustion after 5 days of supplementation with simple sugars (CHO). Finally, after a further 2 wk, they again cycled to exhaustion after 5 days of Cr supplementation. Muscle samples were taken at rest before exercise, at the time point of exhaustion in visit 1, and at subsequent visit time of exhaustion. There was a treatment effect on muscle total Cr content in Cr compared with N and CHO supplementation (P < 0.01). Resting muscle glycogen content was elevated above N following CHO (P < 0.05) but not after Cr. At exhaustion following N, glycogen content was no different from CHO and Cr measured at the same time point during exercise. Cr supplementation under conditions of controlled habitual dietary intake had no effect on muscle glycogen content at rest or after exhaustive exercise. We suggest that any Cr-associated increases in muscle glycogen storage are the result of an interaction between Cr supplementation and other mediators of muscle glycogen storage.
Assuntos
Bebidas Gaseificadas , Creatina/farmacologia , Carboidratos da Dieta/farmacologia , Suplementos Nutricionais , Exercício Físico , Glicogênio/metabolismo , Contração Muscular , Músculo Esquelético/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Administração Oral , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal , Creatina/administração & dosagem , Creatina/metabolismo , Estudos Cross-Over , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/metabolismo , Humanos , Masculino , Fadiga Muscular , Músculo Esquelético/metabolismo , Fosfocreatina/metabolismo , Valores de Referência , Fatores de TempoRESUMO
Maintaining hyperinsulinemia (approximately 150 mU/l) during steady-state hypercarnitinemia (approximately 550 micromol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 x 500-ml solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 x 500 ml of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P < 0.001) and in a lower plasma TC concentration throughout the CHO visit (P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 +/- 10.7 vs. 212.1 +/- 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 +/- 18.0 to 281.0 +/- 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 +/- 9.2 to 166.8 +/- 17.3 mg after 3 days (P < 0.01), which was less than during the Con trial (P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.