Reduction in CVD risk in children by physical activity

描述(由申请人提供)：儿童超重是成人肥胖的强烈预测因素。糖和脂平衡的异常与体重增加和代谢综合征的许多变化有关。久坐肥胖的成年人，特别是肥胖的非裔美国人，更容易出现高血糖、高胰岛素血症、单位脂肪块吸收后脂肪组织脂解率较低、餐后脂肪分解抑制较差以及血流减少。我们建议实施微透析的新用途，以评估间质葡萄糖和甘油浓度分别作为血糖和脂肪组织脂解的指标，以及持续超过24小时的瘦和肥胖青春期前儿童的脂肪组织血流。假设超重儿童全天表现出较高的间质葡萄糖浓度，基础脂解率降低，餐后对脂解的抑制较差，这些异常将与心血管疾病危险因素的更高患病率相关。此外，16周的体力活动将使超重儿童的血糖和脂肪分解曲线正常化或更接近瘦身，并将导致心血管疾病风险曲线的改善。我们将调查瘦和超重的非裔美国人和高加索儿童(8-10岁；n=80)在16周增加体力活动前后的情况。在静息、禁食和进食条件下，以及在运动反应下，使用微透析法监测腹部皮下脂肪组织的脂肪分解和血糖谱。微透析探头将与对照溶液、一氧化氮合酶抑制剂(L-NMMA)或一氧化氮合酶激活剂(乙酰胆碱)一起灌流，以研究肥胖和非裔美国儿童基础脂肪分解被提议减少的机制。这些研究将确定急性和慢性有氧运动是否能改善瘦和超重儿童的脂解和血糖状况，以及这些有益的变化是否会伴随着心血管疾病危险因素的改善。长期目标是：1)确定超重儿童和成人体内缺乏的相关代谢和循环参数，这些参数使他们面临代谢和心血管疾病的风险；以及2)寻找切实可行的方法来扭转肥胖者的代谢和循环不足，从而减少代谢和心血管疾病的发生率。

DESCRIPTION (provided by applicant): Childhood overweight is a strong predictor of adult obesity. Abnormalities in glucose and lipid homeostasis are associated with body weight gain and many o f the alterations found in the Metabolic Syndrome. Obese sedentary adults, in particular obese African Americans, are more prone to hyperglycemia, hyperinsulinemia, lower rates of post- absorptive adipose tissue lipolysis per unit fat mass, poor post- prandial suppression of lipolysis and reduced blood flow. We propose to implement the novel use of microdialysis to assess interstitial glucose and glycerol concentrations as indices of blood glucose and adipose tissue lipolysis, respectively, and adipose tissue blood flow in lean and obese prepubescent children continuously over 24 hours. The hypothesis is that overweight children exhibit higher interstitial glucose concentrations throughout the day, reduced rates of basal lipolysis and poor postprandial suppression of lipolysis compared to lean children, and that these abnormalities will be associated with a higher prevalence of cardiovascular disease risk factors. Furthermore, 16- weeks of physical activity will normalize, or bring closer to lean, the glucose and lipolytic profiles of overweight children and will result in an improved cardiovascular disease risk profile. We will investigate lean and overweight African American and Caucasian children (8- 10 yr; n=80) before and after 16 weeks of increased physical activity. Subcutaneous abdominal adipose tissue lipolysis and glucose profiles will by monitored using microdialysis under resting fasting and fed conditions as well as in response to exercise. Microdialysis probes will be perfused with either a control solution, an inhibitor of nitric oxide synthase (L- NMMA), or an activator of nitric oxide synthase (acetylcholine) to investigate the mechanism of the proposed reduction of basal lipolysis in obese and African American children. These investigations will determine if acute and chronic aerobic physical activity improves the lipolytic and glucose profiles in lean and overweight children, and whether these beneficial changes will be accompanied by improvements in cardiovascular disease risk factors. The long- term objectives are: 1) to identify the relevant in- vivo metabolic and circulatory parameters that are deficient in overweight children and adults that place them at risk for metabolic and cardiovascular disease; and 2) to find practical means of reversing metabolic and circulatory insufficiencies in obese individuals, thereby reducing the incidence of metabolic and cardiovascular diseases.