EFFECT OF OBESITY CONTROL ON GROWTH

肥胖对成人和儿童都是一个严重的健康问题。肥胖儿童的数量一直在增加，现在美国所有儿童中有25%被认为明显超重。由于体重减轻与线性生长速度的下降有关，因此有必要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肥胖增加血浆瘦素浓度的假设来检验营养与生长之间的生理关系，从而增加分泌的生长激素（GH）的生物活性，从而产生过度生长和骨骼成熟。尽管生长迅速，肥胖儿童在生理上和刺激后循环生长激素浓度较低。由于生长激素作为一种具有不同生物活性和标准免疫测定中不同检出率的同种异构体家族循环，因此儿童的快速生长可能是生长激素分泌的一种具有有限免疫活性的高生物活性形式的结果。在这项研究中，一种与人类血清相关的新型生长激素生物测定法将用于确定肥胖儿童的生长激素生物活性是否高于瘦子，以及这种生物活性是否会随着体重减轻而降低。胰岛素样生长因子- i （IGF-I）作用于生长激素，并可能通过负反馈循环减少生长激素的分泌。据报道，肥胖儿童的igf - 1浓度正常或升高的情况各不相同。据报道，肥胖儿童的igf - 1浓度正常或升高的情况各不相同。IGF-I的生物利用度可由一系列igf结合蛋白控制，其浓度可随营养状态而变化。我们将通过评估结合的和游离的IGF-I及其结合蛋白来确定肥胖和瘦弱儿童中生长激素生物活性和IGF-I活性之间的关系。脂肪细胞产物，瘦素，可以作为儿童整体肥胖的指标。瘦素也被认为可以调节食欲，并可能促进青春期的成熟。下丘脑和卵巢中瘦素受体的存在表明，瘦素可能会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、生长激素生物活性、IGF-I有效性和生长之间的相关性。最后，节食对生长速率的影响研究还不完全。作为这项研究的一部分，将确定明智的卡路里限制对肥胖儿童生长速度的影响。在所有的研究中，肥胖女孩在短期显著减少热量摄入和6个月的热量限制以维持体重后，将在喂食状态下进行激素检测。瘦弱的孩子将作为对照（仅在联邦政府研究）。如果我们的假设是正确的，瘦素的变化应该与生长激素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.