EFFECT OF OBESITY CONTROL ON GROWTH

肥胖是一个严重的健康问题，成人和儿童一样。 患有肥胖症的儿童数量一直在增加，使得美国所有儿童中的25%现在被认为明显超重。 由于体重减轻与线性增长率下降有关，因此必须更好地了解营养与控制生长的激素轴之间的关系。 本研究的目的是通过检验儿童期肥胖增加血浆瘦素浓度，从而增加分泌的生长激素（GH）的生物活性以产生过度生长和骨成熟的假设来检验营养和生长之间的生理关系。 尽管他们的快速增长，肥胖儿童有低循环GH浓度的生理和刺激后。 由于GH作为具有不同生物活性和标准免疫测定中不同检出率的同种型家族循环，因此儿童快速生长可能是分泌具有有限免疫活性的高生物效价形式GH的结果。 在本研究中，将使用一种与人血清中使用相关的新型GH生物测定法来确定肥胖儿童中的GH生物活性是否高于瘦型受试者，以及这种生物效价是否会随着体重减轻而降低。胰岛素样生长因子-I（IGF-I）通过负反馈回路抑制GH分泌。 据报道，肥胖儿童的IGF-I浓度正常或升高。据报道，肥胖儿童的IGF-I浓度正常或升高。 IGF-I的生物利用度可以通过一系列IGF结合蛋白来控制，这些蛋白的浓度可以随营养状态而变化。 我们将通过评估结合和游离IGF-I及其结合蛋白，确定肥胖和瘦型儿童GH生物活性和IGF-I活性之间的关系，作为营养的函数。 脂肪细胞产物瘦素可以作为儿童总体肥胖的指标。 瘦素还被认为可以调节食欲，并可能促进青春期成熟。 下丘脑和卵巢中存在瘦素受体，表明瘦素可增加促性腺激素或雌二醇的产生，从而促进生长。 一种新的人血清瘦素测定法将用于确定肥胖、GH生物活性、IGF-I可用性和生长之间的相关性。 最后，节食对生长速度的影响还没有完全研究过。 作为这项研究的一部分，将确定明智的热量限制对肥胖儿童生长速度的影响。 在所有研究中，肥胖女孩将在进食状态下，在短期显着减少热量后，以及在6个月的热量限制以维持体重后进行激素测定。 瘦儿童将作为对照组（仅在进食状态下进行研究）。 如果我们的假设是正确的，瘦素的变化应与GH生物活性的变化呈正相关。

Obesity is a serious health problem in adults and children alike. The number of children with obesity has been increasing, such that 25% of all children in the United States are now considered to be significantly overweight. Since weight loss by be associated with a decrease in linear growth rate, it is essential to better understand the relationship between nutrition and the hormone axes that control growth. The purpose of this research is to examine the physiological relationships between nutrition and growth by testing the hypothesis that obesity in childhood increases plasma leptin concentration which in turn increases the bioactivity of secreted growth hormone (GH) to produce excessive growth and bone maturation. Despite their rapid growth, obese children have low circulating GH concentrations physiologically and after provocative stimulation. Since GH circulates as a family of isoforms which have varying biological activity and varying detection rates in standard immunoassays, it is possible that rapid growth in children is the consequence of secretion of a highly biopotent form of GH with limited imunoactivity. In this research, a novel bioassay for GH relevant for use in human serum will be used to determine whether GH bioactivity is greater in obese children than in lean subjects and whether this biopotency can be reduced with weight loss. Insulin-like growth factor-I (IGF-I) medicates GH action and may decrease GH secretion through a negative feedback loop. IGF-I concentrations have variably been reported to be normal or increased in children with obesity. IGF-I concentrations have variably been reported to be normal or increased in children with obesity. IGF-I bioavailability can be controlled by a series of IGF-binding proteins whose concentrations may change with nutritional state. We will determine the relationship between GH bioactivity and IGF-I activity in obese and lean children as a function of nutrition by assessing bound and free IGF-I and its binding proteins. The fat cell product, leptin, may serve as an indicator of overall adiposity in children. Leptin is also thought to regulate appetite and may be permissive for pubertal maturation. The presence of leptin receptors in hypothalamus and ovary suggests that leptin may increase gonadotropin or estradiol production which may then facilitate growth. A new leptin assay for human serum will be used to determine correlations between adiposity, GH bioactivity, IGF-I availability, and growth. Finally, the effects of dieting on growth rate have been studied incompletely. As part of this study, the effects of judicious calorie restriction on growth rate in obese children will be determined. In all studies, obese girls will have hormone determinations in the fed state, after a short-term marked reduction in calories, and after a 6 month period of caloric restriction for weight maintenance. Lean children will serve as controls (studied in the fed state only). If our hypothesis is correct, changes in leptin should be positively correlated with changes in GH bioactivity.