Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are "exercise resistant", and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the "exercise resistant" phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFβ signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.
Mittwoch, 3. Juli 2013
Science: Blood doping, the flip side of transfusion and transfusion alternatives.
Blood doping in sports has been a hot topic of present. Longitudinal follow up of hematological parameters in different endurance sports, during the 1990s and early 2000s, has provided considerable suspicions about extensive blood manipulation, with performance enhancing effects. Recent doping revelations in the media also prove that blood doping is not an anticipated myth but it is, in fact, real. Erythropoiesis stimulating agents and autologous blood transfusions are used in synergy with substantial effect on the maximum oxygen uptake and delivery to muscles. Whilst both methods of blood manipulation represent a potential health hazard, in the context of an elevated hematocrit, nevertheless despite a number of suspicious deaths amongst athletes, this has not yet been fully documented. A reliable test for detection of recombinant human erythropoietin was implemented in 2000, but this is probably circumvented by microdose regimens. The Athlete's Biological Passport represents the progeny of the idea of an indirect approach based on long term monitoring of hematological parameters, thus making it possible to detect autologous blood doping and erythropoietin use after the substance is excreted. Nevertheless with advances in anti-doping measures it is possible that the levels of excretion of substances used can be masked. Clearly more sensitive and specific diagnostic tools and research/development in these areas of major concern are warranted, which, combined with changes in the athlete's attitude, will help in reaching the vision of fair play.
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