EXERCISE AND OXIDATIVE STRESS MECHANISMS

代谢综合征是一组代谢异常[肥胖、血脂异常、高血压] 和高血糖症]易导致2型糖尿病发病率和心血管死亡率增加。 令人担忧的是，MS的发病率在儿童和青少年中正在不知不觉地增加， 在未来，心血管和代谢疾病的水平将达到前所未有的水平， 惊人的发病率和社会成本。MS的许多发病机制尚不清楚，但氧化 应激（OS），活性氧（ROS）的产生和抗氧化防御之间的不平衡， 正在成为一个主要的潜在机制。虽然体力活动和营养是众所周知的自然 发生的ROS生产和抗氧化防御修饰剂，在儿童的关键机制， 运动，饮食和氧化途径之间的相互作用，以及这些变量对发病的影响 和MS的合并症，还有待研究。我们研究的基本前提是， 缺乏体力活动、高脂肪饮食和肥胖都共同损害儿童OS的调节。这 一般假设可以使用运动作为可量化和可重复的实验来测试， 扰动，由于其独特的能力，刺激，即使在短暂的较量，两个主要来源的活性氧- 线粒体O2流和中性粒细胞（后者，现在已知的应激/炎症反应的一部分， 发生在孩子身上）。我们认为，这些关键机制中的每一个（缺乏体力活动，高脂肪 饮食，肥胖）损害ROS生成和抗氧化防御之间的平衡，使儿童 更容易受到操作系统的破坏性影响。儿童将受到专门设计的运动的挑战 方案，而所有与氧化活性（脂质，葡萄糖，蛋白质， 一氧化氮，DNA;中性粒细胞氧化活性和基因表达，全身抗氧化剂水平）， 同时监测。将检验以下具体假设：a）即使在健康儿童中， 运动过程中氧化过程的显著影响是由性别、成熟状态和 身体健康程度; B）由高脂肪膳食引起的短暂性高脂血症可以急性地和 可测量地增加运动诱导的氧化应激;和c）儿童肥胖和代谢 综合征与过度休息和运动诱导的氧化应激有关。PPG是 非常适合这个具有挑战性的项目，结合了儿科和糖尿病运动的经验， 我们的人体性能实验室和代谢核心测试，具有氧化标记物方面的专业知识 分析三个不同的实验室，所有合作的项目。基于新的和令人兴奋的初步 这项研究的目的是确定这些以前未探索的机制，优化使用 运动和饮食，无论是诊断和治疗，以防止或减轻有害的健康 儿童代谢综合征的后果。

The metabolic syndrome (MS) is a cluster of metabolic abnormalities [obesity, dyslipidemia, hypertension and hyperglycemia] predisposing to increased incidence of type 2 diabetes and cardiovascular mortality. Alarmingly, the incidence of the MS is insidiously increasing among children and adolescents, setting the stage for unprecedented levels of cardiovascular and metabolic disease in the future, with then potential for staggering morbidity and social costs. Many pathogenetic aspects of the MS are still unclear, but oxidative stress (OS), an imbalance between production of reactive oxygen species (ROS) and antioxidant defenses, is emerging as a major potential mechanism. While physical activity and nutrition are well known naturally occurring modifiers of ROS production and anti-oxidant defenses, in children key mechanisms governing the interactions among exercise, diet, and oxidative pathways, and the influence of these variables on the onset and comorbidities of the MS, have yet to be investigated. The fundamental premise of our research is that physical inactivity, high-fat diet and obesity all conspire to impair the regulation of OS in children. This general hypothesis can be tested using exercise as a quantifiable and reproducible experimental perturbation, due to its unique ability to stimulate, even in brief bouts, two main sources of ROS-- mitochondrial 02 flow and neutrophils (the latter, part of the stress/inflammatory response now known to occur with exercise in children). We propose that each of these key mechanisms (physical inactivity, high fat diet, obesity) impairs the balance between ROS generation and antioxidant defenses, rendering the child more vulnerable to the damaging effects of OS. Children will be challenged with specially designed exercise protocols, while all major variables associated with oxidative activity (oxidation of lipids, glucose, proteins, nitric oxide, DNA; neutrophil oxidative activity and gene expression, systemic antioxidants levels) will be simultaneously monitored. The following specific hypotheses will be tested: a) that even in the healthy child, a marked influence on oxidative processes during exercise is exerted by gender, maturational status and degree of physical fitness; b) that the transient hyperlipidemia caused by a high fat meal can acutely and measurably increase exercise-induced oxidative stress; and c) that pediatric obesity and metabolic syndrome are associated with exaggerated resting and exercise-induced oxidative stress. The PPG is uniquely suited for this challenging project, combining the experiences in pediatric and diabetic exercise testing of our human performance laboratory and metabolic core, with the expertise in oxidative marker analysis of three different laboratories, all collaborating in the project. Based on new and exciting preliminary studies, this research is aimed at defining these previously unexplored mechanisms, optimizing the use of exercise and diet, both diagnostically and therapeutically, to prevent or attenuate the deleterious health consequences of the metabolic syndrome in children.