EXERCISE TRAINING IN CHILDREN: MECHANISM OF ALLAYING INFLAMMATION IN OBESITY

儿童运动训练：减轻肥胖炎症的机制

• 批准号: 8616386
• 负责人: PIETRO R GALASSETTI
• 金额: $ 20.13万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8616386
• 关键词: Acute; Affect; African American; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Atherosclerosis; Attenuated; Biological; Biological Markers; Biological Process; Blood Vessels; Body Composition; Cardiovascular Diseases; Cell Culture Techniques; Cell physiology; Cells; Child; Childhood; Chronic; Chronic Disease; Clinical; Development; Diabetes Mellitus; Disease; Dual-Energy X-Ray Absorptiometry; Dyslipidemias; Educational Intervention; Educational Status; Epidemic; Epigenetic Process; Equilibrium; Exercise; Frequencies; Functional disorder; Gases; Genomics; Goals; Health; Health Benefit; Health Care Costs; Hispanics; Homeostasis; Hypoxia; Immune; Impaired cognition; Impairment; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Intervention; Investigation; Knowledge; Lasers; Life; Light; Link; Measurement; Measures; Metabolic; Metric; Natural Immunity; Nature; Obesity; Obstructive Sleep Apnea; Outcome; Oxidative Stress; Participant; Pathogenesis; Pathology; Patients; Phenotype; Physical activity; Physiological; Play; Population; Preventive; Recommendation; Regulation; Research; Resources; Rest; Risk; Role; Severities; Sleep; Sleep Apnea Syndromes; Staging; Stimulus; Stress; Testing; Training; Training Programs; Vasodilation; Whole Organism; Work; base; carbohydrate metabolism; clinical application; clinically relevant; cohort; cytokine; design; disorder risk; dosage; endothelial dysfunction; experience; glycemic control; high risk; improved; in vivo; innovation; insight; lifestyle intervention; meetings; monocyte; neutrophil; novel; obesity in children; obesity risk; prevent; programs; response; sedentary; stem; success

It is now well recognized that inflammatory mediators and innate immune cells play essential roles in the development and progression of atherosclerosis. With the ongoing epidemic of childhood obesity (a chronic inflammatory state), precursors of atherosclerosis are becoming alarmingly apparent in the pediatric population. There is a profound gap in our understanding of: 1) mechanisms that set the stage for atherosclerosis later in life, and 2) how to prevent obesity-related vascular damage at the earliest stages. New insights suggest that physical activity ameliorates endothelial damage in part through the effect of exercise on neutrophils and monocytes, first-responding cells of innate immunity. Using a 10-week exercise-training intervention, one tailored to the capabilities of the child, we will test the following hypotheses in obese children: 1) neutrophil and monocyte genomic and epigenetic regulation and accompanying biological functions are excessively pro-inflammatory, even at rest; 2) the exercise- training program will attenuate pro-inflammatory and intensify anti-inflammatory profiles of these cells; 3) the exercise training reversal of deleterious effects of obesity in neutrophils and monocytes will parallel key physiological changes at the systemic, whole-organism level. Our recruitment is designed to include lower SES children who are at increased risk for obesity and its complications. To elucidate underlying cellular mechanisms, we will study how obesity-related impairments in the cellular milieu (altered carbohydrate metabolism and dyslipidemia) affect neutrophil and monocyte function. This will be accomplished by using brief bouts of exercise as an in vivo acute cell stimulus combined with in vitro cell culture studies. The investigation of neutrophils and monocytes will be accompanied by robust metrics of systemic physiological function and adaptability to training using sophisticated measures of the gas exchange response to exercise and DXA assessments of body composition. Using innovative, noninvasive tests of vascular reactivity (laser-doppler measurement of post-occlusive vasodilation), we will indirectly estimate endothelial function in a way that is feasible in children. Finally, it is increasingly recognized that episodic hypoxia [the result of sleep-disordered breathing (SDB) and obstructive sleep apnea] exacerbates inflammation, is common in obese children, and plays a major role in the many health and cognitive impairments associated with childhood obesity. Consequently, we will use state-of-the-art sleep studies to gauge SDB in our cohort and determine its interaction with the cellular and systemic response to the exercise training intervention. Despite many efforts to implement broad programs of physical activity and other lifestyle interventions, pediatric obesity remains an intractable problem. Our considerable experience in this field suggests the need for targeted approaches that: 1) identify specific disease risk mechanisms, and 2) demonstrate an impact of the proposed intervention on those mechanisms. The results of the proposed research will help channel scarce resources toward the obese children with the greatest need.

现在已经充分认识到，炎症介质和先天性免疫细胞在炎症反应中起重要作用。 动脉粥样硬化的发展和进展。随着儿童肥胖症（一种慢性 炎症状态），动脉粥样硬化的前体在儿童中变得惊人地明显。 人口我们对以下问题的理解存在深刻的差距：1）为以下问题奠定基础的机制 动脉粥样硬化在以后的生活中，和2）如何防止肥胖相关的血管损伤在早期阶段。新 有观点认为，体力活动改善内皮损伤的部分原因是运动对血管内皮细胞的影响。 中性粒细胞和单核细胞，先天免疫的第一反应细胞。通过为期10周的运动训练 干预，一个量身定制的儿童的能力，我们将测试以下假设在肥胖儿童： 1)嗜中性粒细胞和单核细胞基因组和表观遗传调节以及伴随的生物学功能， 过度促炎，即使在休息; 2）运动训练计划将减弱促炎 并加强这些细胞的抗炎作用; 3）运动训练逆转了 嗜中性粒细胞和单核细胞的肥胖将与系统性、整个机体的关键生理变化平行， 水平我们的招募旨在包括社会经济地位较低的儿童，他们患肥胖症的风险较高， 并发症为了阐明潜在的细胞机制，我们将研究肥胖相关的损伤是如何在 细胞环境（改变的碳水化合物代谢和血脂异常）影响中性粒细胞和单核细胞功能。 这将通过使用短暂的运动作为体内急性细胞刺激结合体内刺激来实现。 体外细胞培养研究。中性粒细胞和单核细胞的研究将伴随着稳健的指标 的系统生理功能和适应性训练使用复杂的措施的气体 交换对运动的反应和身体成分的DXA评估。使用创新的，非侵入性的 血管反应性测试（闭塞后血管舒张的激光多普勒测量），我们将间接 以一种在儿童中可行的方式评估内皮功能。最后，人们日益认识到， 发作性缺氧[睡眠呼吸障碍（SDB）和阻塞性睡眠呼吸暂停的结果]会加剧 炎症，是常见的肥胖儿童，并发挥了许多健康和认知的主要作用， 与儿童肥胖症有关的缺陷。因此，我们将使用最先进的睡眠研究， 在我们的队列中测量SDB，并确定其与运动训练的细胞和全身反应的相互作用 干预尽管许多人努力实施广泛的体育活动和其他生活方式计划， 然而，尽管采取了各种干预措施，儿童肥胖仍然是一个棘手的问题。我们在这一领域的丰富经验 表明需要有针对性的方法：1）确定特定的疾病风险机制，2） 说明拟议的干预措施对这些机制的影响。建议的结果 研究将有助于将稀缺的资源用于最需要的肥胖儿童。