Molecular Mechanisms Of Glucose Uptake In Skeletal Muscle At Rest And In Response To Exercise

Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake.Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes.This transporter migrates to the plasma membrane and assists in glucose internalization.However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels.Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.23especia

DISTANCE COVERED IN DIFFERENT GAME SITUATIONS BY HIGHLEVEL BASKETBALL PLAYERS FROM BRAZIL

The aim of this study was to propose a way to classify four different game situations in a basketball game and quantify the covered distances by player positions in each category, using a video-based system. One game of the season 2011/2012 New Basketball Brazil was analyzed. The data on distance covered by the players on both teams was obtained with a video-based manual tracking method (Dvideo System). The game situations were classified as: attack, defense, transition to attack or transition to defense. The distances covered are shown by each player’s position. Significant differences were observed between attack and defense vs. transition to attack and transition to defense, and also for transition to attack vs. transition to defense

Strength Training Prevents Hyperinsulinemia, Insulin Resistance, And Inflammation Independent Of Weight Loss In Fructose-fed Animals

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The aim of this study was to compare the effects of aerobic, strength, and combined training on metabolic disorders induced by a fructose-rich diet. Wistar rats (120 days old) were randomized into five groups (n = 8-14): C (control diet and sedentary), F (fed the fructose-rich diet and sedentary), FA (fed the fructose-rich diet and subject to aerobic exercise), FS (fed the fructose-rich diet and subject to strength exercise), and FAS (fed the fructose-rich diet and subject to combined aerobic and strength exercises). After the 8-week experiment, glucose homeostasis, blood biochemistry, tissue triglycerides, and inflammation were evaluated and analyzed. The strength protocol exerted greater effects on glucose homeostasis, insulin sensitivity, and liver lipid contents than other protocols (all P < 0.05). All three exercise protocols induced a remarkable reduction in inflammation, tissue triglyceride content, and inflammatory pathways, which was achieved through c-Jun NH2-terminal kinase (JNK) phosphorylation and factor nuclear kappa B (NFkB) activation in both the liver and the muscle. Our data suggest that strength training reduced the severity of most of the metabolic disorders induced by a fructose-rich diet and could be the most effective strategy to prevent or treat fructose-induced metabolic diseases.6Brazilian foundation FAPESP [2013/20293-2, 2013/21491-2, 2016/14380-8]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Role of physical exercise in the UPRmt in skeletal muscle

Orientador: Eduardo Rochete RopelleDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências AplicadasResumo: A UPRmt, do inglês mitochondrial unfolded protein response, é uma resposta adaptativa ao estresse, que assegura a integridade e função de proteínas mitocondriais por estimular a atividade de chaperonas (como a HSP60) e proteases mitocondriais (como ClpP). Estudos mutagênicos revelaram que a alteração no equilíbrio estequiométrico entre proteínas codificadas pelo DNA mitocondrial (mtDNA), como a MTCO1, e proteínas da cadeia transportadora de elétrons oriundas do DNA nuclear (nDNA), como SDHA ou ATP5A, ativa a UPRmt. Em organismos como C.elegans e Drosophila, tal resposta aumenta a função mitocondrial, o metabolismo celular e a longevidade através da UPRmt. Tratamentos farmacológicos (como doadores de NAD+ ou ativadores de SIRT1) também ativam esta resposta, aumentando função e biogênese mitocondrial, a capacidade oxidativa de músculo esquelético e fígado, e ainda melhoram sua capacidade funcional. Ainda que a indução da UPRmt mediada pelo desequilíbrio mitonuclear aparentemente seja um processo biológico conservado entre mamíferos, aumentando a função orgânica em diferentes tecidos, ainda não foi explorado se o exercício físico (que aumenta os níveis de NAD+ e ativa SIRT1 e outras vias de biogênese mitocondrial) é capaz de ativar esta resposta ao estresse. Portanto, o objetivo do presente estudo foi avaliar o conteúdo proteico de marcadores da UPRmt e o desequilíbrio mitonuclear no gastrocnêmio de camundongos treinados, bem como sua função mitocondrial. Para tal, foram utilizados camundongos C57BL/6J machos, alocados em grupo controle ou treinado (4 semanas de corrida em esteira). As amostras foram avaliadas por Western-blotting e por respiração mitocondrial. As análises de bioinformática foram realizadas por meio da base de dados genenetwork.org, utilizando dados da musculatura esquelética de linhagens BXD e de humanos. Em camundongos, os marcadores da UPRmt apresentaram forte correlação com genes mitocondriais (também observada na base de dados de humanos) e com fenótipos relacionados à adaptações geradas pelo exercício físico, como RER e atividade locomotora. Os animais treinados aumentaram sua performance, seus níveis de respiração mitocondrial, tiveram aumento de 2 vezes na razão MTCO1:SDHA (desequilíbrio mitonuclear) e aumento do conteúdo proteico de ClpP. Este projeto pode auxiliar na compreensão do papel da UPRmt sobre diversas adaptações desencadeadas pelo exercício físico e na busca por terapias para doenças originadas na disfunção mitocondrialAbstract: The mitochondrial unfolded protein response (UPRmt) is an adaptive stress response, which ensures both integrity and function of proteins by stimulating mitochondrial chaperones (such as HSP60) and mitochondrial proteases (such as ClpP). Mutagenic studies revealed that alterations in the stoichiometric ratio between mtDNA encoded proteins (such as MTCO1) and nDNA OXPHOS subunits of the electron transport chain, such as SDHA or ATP5A, activates the UPRmt. In organisms such as C.elegans and Drosophila, this response enhances mitochondrial function, cell metabolism and longevity through activation of the UPRmt. Pharmacological treatments (such as NAD + boosters or SIRT1 activators) also activate this response, increasing mitochondrial biogenesis and function, oxidative capacity of skeletal muscle and liver and even improves their functional capacity. Although the induction of UPRmt, mediated by mitonuclear imbalance, seems to be a well-conserved biological process among mammals (by increasing the organic function in different tissues), it has not yet been explored if exercise (which increases the NAD+ levels, SIRT1 activity and triggers other pathways promoting mitochondrial biogenesis) is able to activate such stress response. Therefore, the aim of this study was to evaluate the protein content of UPRmt markers and the mitonuclear imbalance in the gastrocnemius of trained mice, as well as mitochondrial function. For this purpose, C57BL/6J mice were allocated into control or trained groups (4 weeks of treadmill running). Skeletal muscle samples were analyzed by Western blotting and mitochondrial respiration. Bioinformatics analysis was performed using genenetwork.org database, with data from skeletal muscle of human and BXD strains. In mice, the UPRmt markers were strongly correlated with mitochondrial genes (also observed in human database) and exercise-related phenotypes, such as RER and locomotor activity. The trained animals increased their exercise performance, their mitochondrial respiration, presented mitonuclear imbalance (2-fold increase in the MTCO1:SDHA ratio) and increased ClpP protein content. This project can assist in understanding the role of UPRmt on several exercise-induced adaptations and provide useful knowledge for future therapies targetting diseases related to mitochondrial dysfunctionMestradoMetabolismo e Biologia MolecularMestre em Ciências da Nutrição e do Esporte e Metabolismo2015/06463-8FAPES

Strength Training Prevents Hyperinsulinemia, Insulin Resistance, and Inflammation Independent of Weight Loss in Fructose-Fed Animals

The aim of this study was to compare the effects of aerobic, strength, and combined training on metabolic disorders induced by a fructose-rich diet. Wistar rats (120 days old) were randomized into five groups (n = 8–14): C (control diet and sedentary), F (fed the fructose-rich diet and sedentary), FA (fed the fructose-rich diet and subject to aerobic exercise), FS (fed the fructose-rich diet and subject to strength exercise), and FAS (fed the fructose-rich diet and subject to combined aerobic and strength exercises). After the 8-week experiment, glucose homeostasis, blood biochemistry, tissue triglycerides, and inflammation were evaluated and analyzed. The strength protocol exerted greater effects on glucose homeostasis, insulin sensitivity, and liver lipid contents than other protocols (all P < 0.05). All three exercise protocols induced a remarkable reduction in inflammation, tissue triglyceride content, and inflammatory pathways, which was achieved through c-Jun NH2-terminal kinase (JNK) phosphorylation and factor nuclear kappa B (NFkB) activation in both the liver and the muscle. Our data suggest that strength training reduced the severity of most of the metabolic disorders induced by a fructose-rich diet and could be the most effective strategy to prevent or treat fructose-induced metabolic diseases

Physical exercise elicits UPRmt in the skeletal muscle: The role of c-Jun N-terminal kinase

Objective: The mitochondrial unfolded protein response (UPRmt) is an adaptive cellular response to stress to ensure mitochondrial proteostasis and function. Here we explore the capacity of physical exercise to induce UPRmt in the skeletal muscle. Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses. Results: Firstly, RNA sequencing and Western blotting analysis revealed that an acute aerobic session stimulated several mitostress-related genes and protein content in muscle, including the UPRmt markers. Conversely, using a large panel of isogenic strains of BXD mice, we identified that BXD73a and 73b strains displayed low levels of several UPRmt-related genes in the skeletal muscle, and this genotypic feature was accompanied by body weight gain, lower locomotor activity, and aerobic capacity. Finally, we identified that c-Jun N-terminal kinase (JNK) activation was critical in exercise-induced UPRmt in the skeletal muscle since pharmacological JNK pathway inhibition blunted exercise-induced UPRmt markers in mice muscle. Conclusion: Our findings provide new insights into how exercise triggers mitostress signals toward the oxidative capacity in the skeletal muscle