RESUMO
PURPOSE: This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system. METHODS: Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot. RESULTS: After bed rest basal insulin concentration was increased by 53% (P < 0.05), the homeostasis model assessment (HOMA) by 40% (P < 0.05), and serum leptin concentration by 35% (P < 0.05) with no changes in body fat mass. Although the soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05). OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P < 0.05). There was a linear relationship between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and HOMA (r = 0.68, P < 0.05) with bed rest. CONCLUSIONS: One week of bed rest is associated with increased leptin levels without augmenting STAT3 phosphorylation indicating some degree of leptin resistance in skeletal muscle, which can be explained, at least in part, by an elevation of PTP1B protein content in the vastus lateralis muscle.
Assuntos
Repouso em Cama , Leptina/metabolismo , Músculo Esquelético/metabolismo , Transdução de Sinais , Adulto , Estudos de Casos e Controles , Humanos , Leptina/sangue , Masculino , Músculo Esquelético/fisiologia , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
The aim was to test the hypothesis that 7 days of bed rest reduces mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after bed rest. Twelve young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from six of the subjects prior to, immediately after, and 3 h after 45 min of one-legged knee extensor exercise performed before and after bed rest. Maximal oxygen uptake decreased by 4%, and exercise endurance decreased nonsignificantly, by 11%, by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content â¼45%, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activity â¼8%, and miR-1 and miR-133a content â¼10%. However, cytochrome c and vascular endothelial growth factor (VEGF) protein content as well as capillarization did not change significantly with bed rest. Acute exercise increased AMP-activated protein kinase phosphorylation, peroxisome proliferator activated receptor-γ coactivator-1α, and VEGF mRNA content in skeletal muscle before bed rest, but the responses were abolished after bed rest. The present findings indicate that only 7 days of physical inactivity reduces skeletal muscle metabolic capacity as well as abolishes exercise-induced adaptive gene responses, likely reflecting an interference with the ability of skeletal muscle to adapt to exercise.
Assuntos
Exercício Físico/fisiologia , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adulto , Repouso em Cama , Composição Corporal/fisiologia , Citocromos c/genética , Citocromos c/metabolismo , Metabolismo Energético/genética , Humanos , Masculino , Mitocôndrias/genética , Consumo de Oxigênio/genética , RNA Mensageiro/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α plays a role in regulation of several metabolic pathways. By use of whole body PGC-1α knockout (KO) mice, we investigated the role of PGC-1α in fasting, acute exercise and exercise training-induced regulation of key proteins in gluconeogenesis and metabolism in the liver. In both wild-type (WT) and PGC-1α KO mice liver, the mRNA content of the gluconeogenic proteins glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was upregulated during fasting. Pyruvate carboxylase (PC) remained unchanged after fasting in WT mice, but it was upregulated in PGC-1α KO mice. In response to a single exercise bout, G6Pase mRNA was upregulated in both genotypes, whereas no significant changes were detected in PEPCK or PC mRNA. While G6Pase and PC protein remained unchanged, liver PEPCK protein content was higher in trained than untrained mice of both genotypes. The mRNA content of the mitochondrial proteins cytochrome c (Cyt c) and cytochrome oxidase (COX) subunit I was unchanged in response to fasting. The mRNA and protein content of Cyt c and COXI increased in the liver in response to a single exercise bout and prolonged exercise training, respectively, in WT mice, but not in PGC-1α KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver, and knockout of PGC-1α had no effect. In conclusion, these results suggest that PGC-1α plays a pivotal role in regulation of Cyt c and COXI expression in the liver in response to a single exercise bout and prolonged exercise training, which implies that exercise training-induced improvements in oxidative capacity of the liver is regulated by PGC-1α.
Assuntos
Jejum/metabolismo , Fígado/metabolismo , Esforço Físico , Transativadores/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Adaptação Fisiológica , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Regulação Enzimológica da Expressão Gênica , Gluconeogênese/genética , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Glicogênio/metabolismo , Camundongos , Camundongos Knockout , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Fosforilação , Piruvato Carboxilase/genética , Piruvato Carboxilase/metabolismo , RNA Mensageiro/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fatores de Tempo , Transativadores/deficiência , Transativadores/genética , Fatores de TranscriçãoRESUMO
Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise training, and describes functional significance of PGC-1alpha-mediated effects in skeletal muscle. In addition, regulation of PGC-1alpha expression and activity in skeletal muscle is described. The impact of changes in PGC-1alpha expression in mouse skeletal muscle and the ability of PGC-1alpha to regulate multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle and concomitant impaired metabolism.
Assuntos
Exercício Físico , Proteínas de Choque Térmico/metabolismo , Contração Muscular , Músculo Esquelético/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Adaptação Fisiológica , Animais , Antioxidantes/metabolismo , Metabolismo Energético , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Humanos , Mediadores da Inflamação/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Processamento de Proteína Pós-Traducional , Comportamento Sedentário , Fatores de Transcrição/genéticaRESUMO
The aim of this study was to test whether the transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)1α regulates the content of pyruvate dehydrogenase (PDH)-E1α and influences PDH activity through regulation of pyruvate dehydrogenase kinase-4 (PDK4) expression and subsequently PDH phosphorylation. PGC-1α whole body knockout (KO), muscle-specific PGC-1α overexpressing mice (MCK PGC-1α), and littermate wild-type (WT) mice underwent two interventions known to affect PDH. Quadriceps muscles were removed from fed and 24-h fasted mice as well as at 6 h of recovery after 1-h running and from mice that did not run acutely. PDH-E1α protein content and PDH-E1α phosphorylation were lower in PGC-1α KO and higher in MCK PGC-1α mice at rest, but, while MCK PGC-1α had higher PDK4 protein content, KO of PGC-1α had no effect on PDK4 protein content. The differences in phosphorylation partly vanished when expressing phosphorylation relative to the PDH-E1α content with only a maintained elevated phosphorylation in MCK PGC-1α mice. Fasting upregulated PDK4 protein in PGC-1α KO, MCK PGC-1α and WT mice, but this was not consistently associated with increased PDH-E1α phosphorylation. Downregulation of the activity of PDH in the active form (PDHa) at 6-h recovery from exercise in both the PGC-1α KO and MCK PGC-1α mice and the association between PDH-E1α phosphorylation and PDHa activity in PGC-1α KO mice indicate that PGC-1α is not required for these responses. In conclusion, PGC-1α regulates PDH-E1α protein content in parallel with mitochondrial oxidative proteins, but does not seem to influence PDH regulation in mouse skeletal muscle in response to fasting and in recovery from exercise.
Assuntos
Piruvato Desidrogenase (Lipoamida)/metabolismo , Músculo Quadríceps/enzimologia , Transativadores/metabolismo , Animais , Ingestão de Alimentos , Jejum , Feminino , Regulação Enzimológica da Expressão Gênica , Glicogênio/metabolismo , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias Musculares/enzimologia , Proteínas Mitocondriais/metabolismo , Contração Muscular , Oxirredução , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Complexo Piruvato Desidrogenase/genética , Complexo Piruvato Desidrogenase/metabolismo , RNA Mensageiro/metabolismo , Recuperação de Função Fisiológica , Fatores de Tempo , Transativadores/deficiência , Transativadores/genética , Fatores de Transcrição , Regulação para CimaRESUMO
The aim was to assess mRNA and/or protein levels of heat shock proteins, cytokines, growth regulating, and metabolic proteins in myalgic muscle at rest and in response to work tasks and prolonged exercise training. A randomized controlled trial included 28 females with trapezius myalgia and 16 healthy controls. Those with myalgia performed ~7 hrs repetitive stressful work and were subsequently randomized to 10 weeks of specific strength training, general fitness training, or reference intervention. Muscles biopsies were taken from the trapezius muscle at baseline, after work and after 10 weeks intervention. The main findings are that the capacity of carbohydrate oxidation was reduced in myalgic compared with healthy muscle. Repetitive stressful work increased mRNA content for heat shock proteins and decreased levels of key regulators for growth and oxidative metabolism. In contrast, prolonged general fitness as well as specific strength training decreased mRNA content of heat shock protein while the capacity of carbohydrate oxidation was increased only after specific strength training.
Assuntos
Exercício Físico/fisiologia , Doenças Musculares/terapia , Estresse Psicológico , Adulto , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica , Glicogênio Sintase/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/metabolismo , Doenças Musculares/fisiopatologia , Oxigênio/metabolismo , Piruvato Desidrogenase (Lipoamida)/metabolismo , RNA Mensageiro/metabolismo , Treinamento Resistido , Resultado do Tratamento , TrabalhoRESUMO
To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both legs before and after a 3-h hyperinsulinemic euglycemic clamp performed 3 h after a 45-min, one-legged exercise. Blood samples were obtained from one femoral artery and both femoral veins before and during the clamp. Glucose infusion rate and leg glucose extraction during the clamp were lower after than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate glycogen synthase (GS) was reduced with normal GS site 3 but abnormal GS site 2+2a phosphorylation after bed rest. Exercise enhanced insulin-stimulated leg glucose extraction both before and after bed rest, which was accompanied by higher GS activity in the prior-exercised leg than the rested leg. The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage.
Assuntos
Repouso em Cama/efeitos adversos , Transportador de Glucose Tipo 4/metabolismo , Glicogênio Sintase/metabolismo , Resistência à Insulina/fisiologia , Benzodiazepinonas , Glicemia , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Regulação da Expressão Gênica/fisiologia , Glucose/administração & dosagem , Transportador de Glucose Tipo 4/genética , Glicogênio/metabolismo , Glicogênio Sintase/genética , Humanos , Insulina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Palmitatos/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
PURPOSE: The study's purpose was to examine the effects of a short-term period with intensified training or training cessation of trained soccer players on VO(2) kinetics at 75% maximal aerobic speed, oxidative enzymes, and performance in repeated high-intensity exercise. METHODS: After the last match of the season, 18 elite soccer players were, for a 2-wk period, assigned to a high-intensity training group (n = 7) performing 10 training sessions mainly consisting of aerobic high-intensity training (8 × 2 min) and speed endurance training (10-12 × 30-s sprints) or a training cessation group (n = 11) that refrained from training. RESULTS: For the training cessation group, VO(2) kinetics became slower (P < 0.05) with a larger time constant (τ = 21.5 ± 2.9 vs 23.8 ± 3.2 s (mean ± SD, before vs after)) and a larger mean response time (time delay + τ = 45.0 ± 1.8 vs 46.8 ± 2.2 s). The amount of muscle pyruvate dehydrogenase (17%, P < 0.01) and maximal activity of citrate synthase (12%) and 3-hydroxyacyl-CoA (18%, P < 0.05) were lowered. In addition, the fraction of slow twitch fibers (56% ± 18% vs 47% ± 15%, P < 0.05), Yo-Yo intermittent recovery level 2 test (845 ± 160 vs 654 ± 99 m), and the repeated sprint performance (33.41 ± 0.96 vs 34.11 ± 0.92 s, P < 0.01) were reduced. For the high-intensity training group, running economy was improved (P < 0.05), and the amount of pyruvate dehydrogenase (17%) and repeated sprint performance (33.44 ± 1.17 vs 32.81 ± 1.01 s) were enhanced (P < 0.05). CONCLUSIONS: Inactivity slows VO(2) kinetics in association with a reduction of muscle oxidative capacity and repeated high-intensity running performance. In addition, intensified training of already well-trained athletes can improve mechanical efficiency and repeated sprint performance.
Assuntos
Desempenho Atlético/fisiologia , Consumo de Oxigênio/fisiologia , Futebol/fisiologia , Adulto , Atletas , Citrato (si)-Sintase/análise , Humanos , Masculino , Fibras Musculares de Contração Lenta/metabolismo , Fibras Musculares de Contração Lenta/fisiologia , Resistência Física/fisiologia , Complexo Piruvato Desidrogenase/análise , Corrida/fisiologia , Adulto JovemRESUMO
To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (W(max))] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger (P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger (P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced (P ≤ 0.05) dephosphorylation of PDH-E1α on Ser²9³, Ser²95 and Ser³°°, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.
Assuntos
Repouso em Cama , Exercício Físico , Contração Muscular , Piruvato Desidrogenase (Lipoamida)/metabolismo , Músculo Quadríceps/enzimologia , Adulto , Biópsia , Glicemia/metabolismo , Ativação Enzimática , Teste de Esforço , Regulação Enzimológica da Expressão Gênica , Intolerância à Glucose/sangue , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Ácido Láctico/sangue , Masculino , Consumo de Oxigênio , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase (Lipoamida)-Fosfatase/genética , Piruvato Desidrogenase (Lipoamida)-Fosfatase/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Mensageiro/metabolismo , Serina , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To test the hypothesis that free fatty acid (FFA) and muscle glycogen modify exercise-induced regulation of PDH (pyruvate dehydrogenase) in human skeletal muscle through regulation of PDK4 expression. RESEARCH DESIGN AND METHODS: On two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relative to the contra-lateral leg (CON) the day before the experimental day. On the experimental days, plasma FFA was ensured normal or remained elevated by consuming breakfast rich (low FFA) or poor (high FFA) in carbohydrate, 2 h before performing 20 min of two-legged knee extensor exercise. Vastus lateralis biopsies were obtained before and after exercise. RESULTS: PDK4 protein content was approximately 2.2- and approximately 1.5-fold higher in LOW than CON leg in high FFA and low FFA, respectively, and the PDK4 protein content in the CON leg was approximately twofold higher in high FFA than in low FFA. In all conditions, exercise increased PDHa (PDH in the active form) activity, resulting in similar levels in LOW leg in both trials and CON leg in high FFA, but higher level in CON leg in low FFA. PDHa activity was closely associated with the PDH-E1alpha phosphorylation level. CONCLUSIONS: Muscle glycogen and plasma FFA attenuate exercise-induced PDH regulation in human skeletal muscle in a nonadditive manner. This might be through regulation of PDK4 expression. The activation of PDH by exercise independent of changes in muscle glycogen or plasma FFA suggests that exercise overrules FFA-mediated inhibition of PDH (i.e., carbohydrate oxidation), and this may thus be one mechanism behind the health-promoting effects of exercise.
Assuntos
Exercício Físico/fisiologia , Ácidos Graxos não Esterificados/sangue , Glicogênio/metabolismo , Músculo Esquelético/fisiologia , Complexo Piruvato Desidrogenase/metabolismo , Adulto , Estatura , Peso Corporal , Ácidos Graxos não Esterificados/farmacologia , Humanos , Insulina/sangue , Perna (Membro) , Masculino , Músculo Esquelético/metabolismo , Consumo de Oxigênio , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , Valores de Referência , Suporte de Carga , Adulto JovemRESUMO
To test the hypothesis that pyruvate dehydrogenase (PDH) is differentially regulated in specific human muscles, regulation of PDH was examined in triceps, deltoid, and vastus lateralis at rest and during intense exercise. To elicit considerable glycogen use, subjects performed 30 min of exhaustive arm cycling on two occasions and leg cycling exercise on a third day. Muscle biopsies were obtained from deltoid or triceps on the arm exercise days and from vastus lateralis on the leg cycling day. Resting PDH protein content and phosphorylation on PDH-E1 alpha sites 1 and 2 were higher (P < or = 0.05) in vastus lateralis than in triceps and deltoid as was the activity of oxidative enzymes. Net muscle glycogen utilization was similar in vastus lateralis and triceps ( approximately 50%) but less in deltoid (likely reflecting less recruitment of deltoid), while muscle lactate accumulation was approximately 55% higher (P < or = 0.05) in triceps than vastus lateralis. Exercise induced (P < or = 0.05) dephosphorylation of both PDH-E1 alpha site 1 and site 2 in all three muscles, but it was more pronounced at PDH-E1 alpha site 1 in triceps than in vastus lateralis (P < or = 0.05). The increase in activity of the active form of PDH (PDHa) after 10 min of exercise was more marked in vastus lateralis ( approximately 246%) than in triceps ( approximately 160%), but when it was related to total PDH-E1 alpha protein content, no difference was evident. In conclusion, PDH protein content seems to be related to metabolic enzyme profile, rather than myosin heavy chain composition, and less PDH capacity in triceps is a likely contributing factor to higher lactate accumulation in triceps than in vastus lateralis.
Assuntos
Exercício Físico/fisiologia , Músculo Esquelético/enzimologia , Piruvato Desidrogenase (Lipoamida)/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Descanso/fisiologia , Adulto , Braço , Glicogênio/metabolismo , Humanos , Ácido Láctico/metabolismo , Perna (Membro) , Masculino , Fibras Musculares de Contração Rápida/enzimologia , Fibras Musculares de Contração Lenta/enzimologia , Músculo Esquelético/citologia , FosforilaçãoRESUMO
The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice performed a single treadmill-running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2 h, or 6 h after exercise. Another group of PGC-1alpha KO and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were obtained approximately 37 h after the last training session. Resting muscles of the PGC-1alpha KO mice had lower ( approximately 20%) cytochrome c (cyt c), cytochrome oxidase (COX) I, and aminolevulinate synthase (ALAS) 1 mRNA and protein levels than WT, but similar levels of AMP-activated protein kinase (AMPK) alpha1, AMPKalpha2, and hexokinase (HK) II compared with WT mice. A single exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase-beta and the level of HKII mRNA similarly in WG of KO and WT. In contrast, cyt c mRNA in soleus was upregulated in WT muscles only. Exercise training increased cyt c, COXI, ALAS1, and HKII mRNA and protein levels equally in WT and KO animals, but cyt c, COXI, and ALAS1 expression remained approximately 20% lower in KO animals. In conclusion, lack of PGC-1alpha reduced resting expression of cyt c, COXI, and ALAS1 and exercise-induced cyt c mRNA expression. However, PGC-1alpha is not mandatory for training-induced increases in ALAS1, COXI, and cyt c expression, showing that factors other than PGC-1alpha can exert these adaptations.