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Bente Klarlund Pedersen - One of the best experts on this subject based on the ideXlab platform.
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angiogenin and osteoprotegerin are type ii muscle specific Myokines protecting pancreatic beta cells against proinflammatory cytokines
Scientific Reports, 2018Co-Authors: Sabine Rutti, Rodolphe Dusaulcy, Jakob S Hansen, Cedric Howald, Emmanouil T Dermitzakis, Bente Klarlund Pedersen, M Pinget, Peter PlomgaardAbstract:Tissue cross-talk is emerging as a determinant way to coordinate the different organs implicated in glucose homeostasis. Among the inter-organ communication factors, muscle-secreted Myokines can modulate the function and survival of pancreatic beta-cells. Using primary human myotubes from soleus, vastus lateralis and triceps brachii muscles, we report here that the impact of Myokines on beta-cells depends on fiber types and their metabolic status. We show that Type I and type II primary myotubes present specific mRNA and Myokine signatures as well as a different sensitivity to TNF-alpha induced insulin resistance. Finally, we show that angiogenin and osteoprotegerin are triceps specific Myokines with beta-cell protective actions against proinflammatory cytokines. These results suggest that type I and type II muscles could impact insulin secretion and beta-cell mass differentially in type 2 diabetes through specific Myokines secretion.
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exercise induced muscle derived cytokines inhibit mammary cancer cell growth
American Journal of Physiology-endocrinology and Metabolism, 2011Co-Authors: Pernille Hojman, Christine Dethlefsen, Claus Brandt, Jakob Bondo Hansen, Line Pedersen, Bente Klarlund PedersenAbstract:Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these Myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a Myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more Myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.
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lif is a contraction induced Myokine stimulating human myocyte proliferation
Journal of Applied Physiology, 2011Co-Authors: Christa Broholm, Bente Klarlund Pedersen, Claus Brandt, Matthew J Laye, Radhika Vadalasetty, Henriette Pilegaard, Camilla ScheeleAbstract:The cytokine leukemia inhibitory factor (LIF) is expressed by skeletal muscle and induces proliferation of myoblasts. We hypothesized that LIF is a contraction-induced Myokine functioning in an aut...
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the role of exercise induced Myokines in muscle homeostasis and the defense against chronic diseases
BioMed Research International, 2010Co-Authors: Claus Brandt, Bente Klarlund PedersenAbstract:Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Regular exercise offers protection against type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, and dementia. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the antiinflammatory effect of regular exercise. Here we suggest that exercise may exert its anti-inflammatory effect via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise. According to our theory, such effects may in part be mediated via muscle-derived peptides, so-called “Myokines”. Contracting skeletal muscles release Myokines with endocrine effects, mediating direct anti-inflammatory effects, and/or specific effects on visceral fat. Other Myokines work locally within the muscle and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, Myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced Myokines appear to be involved in mediating both systemic as well as local anti-inflammatory effects.
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muscle as an endocrine organ focus on muscle derived interleukin 6
Physical Review, 2008Co-Authors: Bente Klarlund Pedersen, Mark A. FebbraioAbstract:Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "Myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied Myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a Myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the Myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.
Mark A. Febbraio - One of the best experts on this subject based on the ideXlab platform.
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Muscles, exercise and obesity: Skeletal muscle as a secretory organ
Nature Reviews Endocrinology, 2012Co-Authors: Bente K Pedersen, Mark A. FebbraioAbstract:During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as Myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some Myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other Myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent Myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered Myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.
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muscle as an endocrine organ focus on muscle derived interleukin 6
Physical Review, 2008Co-Authors: Bente Klarlund Pedersen, Mark A. FebbraioAbstract:Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "Myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied Myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a Myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the Myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.
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muscle as an endocrine organ focus on muscle derived interleukin 6
Physical Review, 2008Co-Authors: Bente Klarlund Pedersen, Mark A. FebbraioAbstract:Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as “Myokines.” Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied Myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a Myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin ac...
Yoe-sik Bae - One of the best experts on this subject based on the ideXlab platform.
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Proteomic Analysis of the Palmitate-induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance
Molecular & cellular proteomics : MCP, 2015Co-Authors: Jong Hyuk Yoon, Dayea Kim, Jin-hyeok Jang, Jaewang Ghim, Soyeon Park, Parkyong Song, Yonghoon Kwon, Jaeyoon Kim, Daehee Hwang, Yoe-sik BaeAbstract:Elevated levels of the free fatty acid palmitate are found in the plasma of obese patients and induce insulin resistance. Skeletal muscle secretes Myokines as extracellular signaling mediators in response to pathophysiological conditions. Here, we identified and characterized the skeletal muscle secretome in response to palmitate-induced insulin resistance. Using a quantitative proteomic approach, we identified 36 secretory proteins modulated by palmitate-induced insulin resistance. Bioinformatics analysis revealed that palmitate-induced insulin resistance induced cellular stress and modulated secretory events. We found that the decrease in the level of annexin A1, a secretory protein, depended on palmitate, and that annexin A1 and its receptor, formyl peptide receptor 2 agonist, played a protective role in the palmitate-induced insulin resistance of L6 myotubes through PKC-θ modulation. In mice fed with a high-fat diet, treatment with the formyl peptide receptor 2 agonist improved systemic insulin sensitivity. Thus, we identified Myokine candidates modulated by palmitate-induced insulin resistance and found that the annexin A1- formyl peptide receptor 2 pathway mediated the insulin resistance of skeletal muscle, as well as systemic insulin sensitivity.
Alejandro Lucia - One of the best experts on this subject based on the ideXlab platform.
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Myokine adipokine response to aerobic exercise is it just a matter of exercise load
Frontiers in Physiology, 2019Co-Authors: Ye Tian, Pedro L. Valenzuela, Chuanye Huang, Jiexiu Zhao, Ping Hong, Shuhui Yin, Alejandro LuciaAbstract:Purpose Exercise health benefits are partly mediated by exertional changes in several Myokines/adipokines. This study aimed to compare the acute response of some of these biomarkers to aerobic exercise performed at the intensity corresponding to the maximum fat oxidation rate (FATmax) or the "anaerobic" threshold (AT). Methods Following a cross-over, counterbalanced design, 14 healthy untrained men (23 ± 1 years) performed a 45-min exercise bout at their FATmax or AT intensity (been previously determined through incremental exercise tests). The concentration of interleukin (IL)-15, follistatin, myostatin, fibroblast-growth factor (FGF)-21, irisin, resistin, and omentin was measured at baseline and 0, 1, 3, 24, 48, and 72 h post-exercise. Results AT exercise was performed at a higher intensity (85 ± 8 vs. 52 ± 14% of maximal oxygen uptake [VO2 max], p < 0.001) and induced a higher energy expenditure (p < 0.001) than FATmax, whereas a greater fat oxidation was observed in the latter (p < 0.001). A higher peak response of FGF-21 (+90%, p < 0.01) and follistatin (+49%, p < 0.05) was found after AT-exercise, as well as a trend toward a higher peak level of omentin (+13%, p = 0.071) and a greater decrease in resistin (-16%, p = 0.073). Conclusion Increasing exercise load (from FATmax to AT) results in a higher response of FGF-21, follistatin and omentin to aerobic exercise, with the subsequent potential cardiometabolic benefits. No effects were, however, observed on the remainder of biomarkers. Future research should address if manipulating other exercise variables (e.g., type, frequency) can promote a higher Myokine/adipokine response.
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Myokine/Adipokine Response to “Aerobic” Exercise: Is It Just a Matter of Exercise Load?
Frontiers Media S.A., 2019Co-Authors: Ye Tian, Pedro L. Valenzuela, Chuanye Huang, Jiexiu Zhao, Ping Hong, Shuhui Yin, Alejandro LuciaAbstract:PurposeExercise health benefits are partly mediated by exertional changes in several Myokines/adipokines. This study aimed to compare the acute response of some of these biomarkers to aerobic exercise performed at the intensity corresponding to the maximum fat oxidation rate (FATmax) or the “anaerobic” threshold (AT).MethodsFollowing a cross-over, counterbalanced design, 14 healthy untrained men (23 ± 1 years) performed a 45-min exercise bout at their FATmax or AT intensity (been previously determined through incremental exercise tests). The concentration of interleukin (IL)-15, follistatin, myostatin, fibroblast-growth factor (FGF)-21, irisin, resistin, and omentin was measured at baseline and 0, 1, 3, 24, 48, and 72 h post-exercise.ResultsAT exercise was performed at a higher intensity (85 ± 8 vs. 52 ± 14% of maximal oxygen uptake [VO2 max], p < 0.001) and induced a higher energy expenditure (p < 0.001) than FATmax, whereas a greater fat oxidation was observed in the latter (p < 0.001). A higher peak response of FGF-21 (+90%, p < 0.01) and follistatin (+49%, p < 0.05) was found after AT-exercise, as well as a trend toward a higher peak level of omentin (+13%, p = 0.071) and a greater decrease in resistin (−16%, p = 0.073).ConclusionIncreasing exercise load (from FATmax to AT) results in a higher response of FGF-21, follistatin and omentin to aerobic exercise, with the subsequent potential cardiometabolic benefits. No effects were, however, observed on the remainder of biomarkers. Future research should address if manipulating other exercise variables (e.g., type, frequency) can promote a higher Myokine/adipokine response
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Myokine response to high intensity interval vs resistance exercise an individual approach
Frontiers in Physiology, 2018Co-Authors: Ye Tian, Pedro L. Valenzuela, Chuanye Huang, Jiexiu Zhao, Ping Hong, Shuhui Yin, Alejandro LuciaAbstract:Purpose: This study aimed to compare the response to acute exercise of several Myokines/hormones involved in metabolic function between two types of training sessions that are growing in popularity for their purported cardiometabolic benefits, high-intensity interval (HIIT) and resistance training (RT). Methods: Seventeen healthy, non-athletic men (23 ± 3 years) participated in this cross-over study. They randomly performed a HIIT [with short (HIIT1) or long (HIIT2) intervals] or a RT session. The concentration of fibroblast-growth factor (FGF) 21, follistatin, ghrelin, interleukin-15, irisin, myostatin, and peptide YY was measured at baseline and 0, 1, 3, 24, 48, and 72 h post-exercise. An individual approach was adopted to determine the rate of responsiveness to each specific cytokine and training mode. Results: A significant condition (session type) by time interaction (p = 0.004) effect was observed for FGF21, with RT eliciting a greater area under the curve (AUC) concentration than HIIT1 (p = 0.02). The AUC for follistatin was significantly greater after HIIT2 compared with RT (p = 0.02). Individual responsiveness to all session types ranged between 19 and 93% depending on the cytokine. However, most subjects (71-100%) responded positively for all cytokines (except for irisin, with only 53% of responders) after 1+ session type. Conclusion: Except for FGF21, our results show no overall differences in the Myokine response to HIIT or RT. A considerable individual variability was observed, with some subjects responding to some but not other training session types. Notwithstanding, most responded to at least one training session. Thus, it is mostly the individual response of each subject rather than general recommendations on type of training session (i.e., RT vs. HIIT or HIIT subtypes) that must be taken into consideration for maximizing cardiometabolic benefits in the context of personalized exercise prescription.
Jong Hyuk Yoon - One of the best experts on this subject based on the ideXlab platform.
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Proteomic Analysis of the Palmitate-induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance
Molecular & cellular proteomics : MCP, 2015Co-Authors: Jong Hyuk Yoon, Dayea Kim, Jin-hyeok Jang, Jaewang Ghim, Soyeon Park, Parkyong Song, Yonghoon Kwon, Jaeyoon Kim, Daehee Hwang, Yoe-sik BaeAbstract:Elevated levels of the free fatty acid palmitate are found in the plasma of obese patients and induce insulin resistance. Skeletal muscle secretes Myokines as extracellular signaling mediators in response to pathophysiological conditions. Here, we identified and characterized the skeletal muscle secretome in response to palmitate-induced insulin resistance. Using a quantitative proteomic approach, we identified 36 secretory proteins modulated by palmitate-induced insulin resistance. Bioinformatics analysis revealed that palmitate-induced insulin resistance induced cellular stress and modulated secretory events. We found that the decrease in the level of annexin A1, a secretory protein, depended on palmitate, and that annexin A1 and its receptor, formyl peptide receptor 2 agonist, played a protective role in the palmitate-induced insulin resistance of L6 myotubes through PKC-θ modulation. In mice fed with a high-fat diet, treatment with the formyl peptide receptor 2 agonist improved systemic insulin sensitivity. Thus, we identified Myokine candidates modulated by palmitate-induced insulin resistance and found that the annexin A1- formyl peptide receptor 2 pathway mediated the insulin resistance of skeletal muscle, as well as systemic insulin sensitivity.
