EFFECT OF OBESITY CONTROL ON GROWTH

肥胖控制对生长的影响

• 批准号: 6263658
• 负责人: CAROL M FOSTER
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6263658
• 关键词: caloric dietary content; child (0-11); child physical development; clinical research; hormone binding protein; human subject; insulin; insulinlike growth factor; leptin; nutrition; nutrition related tag; obesity; somatotropin; weight control

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.

肥胖是成人和儿童的严重健康问题。 肥胖儿童的数量一直在增加，因此，美国所有儿童中有25％被认为是显着超重。 由于通过线性生长速率降低而减轻体重，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至关重要。 这项研究的目的是通过检验以下假设来检查营养与生长之间的生理关系，即儿童期肥胖会增加血浆瘦素浓度，从而增加分泌生长激素（GH）的生物活性以产生过度生长和骨成熟。 尽管肥胖的儿童在生理上和挑衅性刺激后的循环GH浓度较低。 由于GH作为一个同工型循环，具有不同的生物学活性和标准免疫测定中检测率不同的同工型，因此儿童的快速生长可能是分泌高度生物体型的GH的结果，其不受度侵入性有限。 在这项研究中，将使用用于人类血清使用的新型生物测定法来确定肥胖儿童的GH生物活性是否比精益受试者更大，并且是否可以随体重减轻而降低这种生物性。胰岛素样生长因子-I（IGF-I）药物GH作用可能会通过负反馈回路减少GH分泌。 据报道，肥胖儿童的IGF-I浓度已正常或增加。据报道，肥胖儿童的IGF-I浓度已正常或增加。 IGF-I生物利用度可以通过一系列IGF结合蛋白来控制，IGF结合蛋白的浓度可能会随营养状态而变化。 我们将通过评估结合和游离的IGF-I及其结合蛋白来确定肥胖儿童和瘦儿童中GH生物活性与IGF-I活性之间的关系。 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，并且可以允许青春期成熟。 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。 针对人血清的新瘦素测定法将用于确定肥胖，GH生物活性，IGF-I的可用性和生长之间的相关性。 最后，未完全研究了节食对生长速率的影响。 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增长率的影响。 在所有研究中，肥胖的女孩在短期降低卡路里后，在加重体重的热量限制6个月后，在美联储状态下的荷尔蒙测定。 精益的孩子将作为控制（仅在美联储州进行研究）。 如果我们的假设是正确的，则瘦素的变化应与GH生物活性的变化呈正相关。