[Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction]. / Regulação do metabolismo de glicose e ácido graxo no músculo esquelético durante exercício físico.

The glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle?

Regulação do metabolismo de glicose e ácido graxo no músculo esquelético durante exercício físico / Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction

O ciclo glicose-ácido graxo explica a preferência do tecido muscular pelos ácidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercício de alta intensidade, há aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espécies reativas de oxigênio (EROs) durante a atividade muscular sugere que o balanço redox intracelular é importante na regulação do metabolismo de lipídios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteína desacopladora mitocondrial. O efeito oposto é esperado durante a atividade moderada. Assim, as questões levantadas nesta revisão são: Por que o músculo esquelético utiliza preferencialmente os lipídios no estado basal e de atividade moderada? Por que o ciclo glicose-ácido graxo falha em exercer seus efeitos durante o exercício intenso? Como o músculo esquelético regula o metabolismo de lipídios e carboidratos em regime envolvendo o ciclo contração-relaxamento.

The glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle?.

Regulação metabólica e produção de espécies reativas de oxigênio durante a contração muscular: efeito do glicogênio na manutenção do estado redox intracelular / Metabolic regulation and production of oxygen reactive species during muscule contraction: effect of glycogen on intracellular redox state

O exercício físico prolongado reduz os estoques de glicogênio muscular. Nessas condições, os processos de fadiga muscular são estimulados coincidindo com um aumento na produção de espécies reativas de oxigênio. A suplementação de carboidratos ou de antioxidantes isoladamente contribui para a melhora da performance muscular, sugerindo um efeito importante da depleção de substrato (glicose) e do aumento da produção de EROs no desenvolvimento da fadiga muscular durante a atividade física. Embora o mecanismo seja desconhecido, estamos propondo neste estudo que uma maior disponibilidade de glicogênio poderia favorecer uma maior atividade da via das pentoses fosfato, aumentando a disponibilidade de NADPH e GSH no tecido muscular esquelético. Uma maior capacidade antioxidante aumentaria a capacidade do tecido muscular em atividade, mantendo o equilíbrio redox durante atividade física prolongada e melhorando o desempenho. Neste processo, o ciclo glicose-ácido graxo pode ser importante aumentando a oxidação de lipídio e reduzindo o consumo de glicogênio durante a atividade prolongada. Além disso, um aumento na produção de EROs pode reduzir a atividade de enzimas importantes do metabolismo celular incluindo a aconitase e a a-cetoglutarato desidrogenase, comprometendo a produção de energia oxidativa, via predominante na produção de ATP durante a atividade muscular prolongada.

Fatigue is closely related to the depletion of glycogen in the skeletal muscle during prolonged exercise. Under this condition, the production of oxygen reactive species (ROS) is substantially increased. It has been shown that dietary supplementation of carbohydrate or antioxidant attenuates muscle fatigue during contraction. This suggests that glycogen availability and/or elevated ROS production plays an important role on muscle fatigue development during prolonged muscle activity. Although the mechanism is still unknown, we propose that elevated muscle glycogen availability may lead to a high activity of hexose monophosphate pathway, increasing the NADPH and glutathione concentration in the skeletal muscle tissue. Elevated antioxidant capacity would increase the muscle redox balance during muscle contraction, improving performance. In this process, the glucose-fatty acid cycle may be important to increase lipid oxidation and consequently decrease glycogen utilization during prolonged activity. In addition, an elevated ROS production could reduce the activity of key metabolic enzymes including aconitase and a-ketoglutarate dehydrogenase, decreasing the oxidative energy production in the skeletal muscle during prolonged activity.

Does exercise training interfere with the effects of L-carnitine supplementation?

OBJECTIVE: We investigated the effect of L-carnitine supplementation on carnitine content in muscle fiber, glucose, and fatty acid metabolism and on performance in trained rats. METHODS: Male Wistar rats received a daily dose of 28 mg/kg, intragastrically, during the last 4 wk of a 6-wk moderate-intensity training program. The contents of carnitine and coenzyme A were evaluated in muscle fiber and its capacity to metabolize labeled glucose, oleate, and pyruvate. The ergogenic effect of the amine was assessed by the evaluation of time until exhaustion in an exercise session. The results were analyzed by analysis of variance and Tukey's post hoc test, and significance was set at P < 0.05. RESULTS: In our model, carnitine supplementation increased time until exhaustion (14.0%), similar to that observed for trained rats, but the effect was even greater (30.3% increase) in the supplemented and trained rats. Carnitine supplementation increased oleate decarboxylation (17% for sedentary rats and 119% for trained rats) and decreased glucose (29.7% and 45% for sedentary and trained rats, respectively) and [2-(14)C ]-pyruvate (45.9% and 61% for sedentary and trained rats, respectively) decarboxylation. The flux of [1-(14)C]-pyruvate through the Krebs cycle increased by 32% and 70% for supplemented sedentary and trained rats, respectively. The training protocol also increased [1-(14)C]-pyruvate decarboxylation by 32%. The cytosolic content of free, long-chain, and short-chain acyl-carnitine increased in the soleus muscle obtained from supplemented sedentary rats by 28%, 117%, and 16%, respectively, and 99%, 205%, and 32% for the muscle from supplemented trained rats. CONCLUSIONS: This study showed that carnitine supplementation increases fatty acid oxidation in skeletal muscle by a mechanism that includes increasing total carnitine content in soleus muscle mitochondria and the total content of acyl-carnitine. The most interesting finding was that the effect of supplementation was even greater in trained rats that had received 3-wk supplementation of carnitine.

Branched-chain amino acid supplementation and the immune response of long-distance athletes.

OBJECTIVE: Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. METHODS: Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. RESULTS: After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. CONCLUSIONS: Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.