EFFECTS OF GROWTH HORMONE ON METABOLISM AND SATIATION IN PRADER-WILLI SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Prader-Willi综合征是一种神经行为综合征，其临床特征包括新生儿发育不良、一种独特的行为表型、认知障碍、低眼压、吞噬功能亢进和病态肥胖。这种综合征是最常见的导致肥胖的遗传原因。有人认为，吞噬功能亢进是下丘脑功能改变的继发性症状，而下丘脑功能改变是这种情况的遗传改变的结果。患有Prader-Willi综合征的儿童有证据表明，继发于下丘脑功能障碍的生长激素缺乏。研究表明，接受生长激素治疗的Prader-Willi综合征儿童脂肪质量减少，瘦体重增加，生长速度和静息能量消耗增加。目前尚不清楚患有Prader-Willi综合征的儿童合并GH的治疗是否会导致下丘脑的变化，或者这种影响是否是外围的。 本研究将探讨生长激素对下丘脑对饥饿和饱腹感的认知，以及对PWS患者基础代谢率和身体成分的影响。我们将在生长激素治疗前和治疗一年后，使用功能磁共振成像比较PWS患者饥饿和饱足的神经解剖学相关性。此外，我们将使用正常体重的兄弟姐妹和非PWS肥胖个体作为额外的对照组。将抽取血液以确定各种荷尔蒙和神经递质水平，有时与这些人的饥饿和饱腹感相关。基础代谢率和身体组成通过双能X射线吸收测量法进行；将对所有个体进行评估，并将在使用生长激素治疗一年后对PWS患者进行重新评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prader-Willi Syndrome is a neurobehavioral syndrome whose clinical features include neonatal failure-to-thrive, a distinct behavioral phenotype, cognitive impairment, hypotonia, hyperphagia and morbid obesity. This syndrome is the most commonly recognized genetic cause of obesity. It has been suggested that the hyperphagia is secondary to altered hypothalamic function, which is a consequence of the genetic alterations that characterize this condition. Children with Prader-Willi syndrome have evidence of a growth hormone deficiency secondary to hypothalamic dysfunction. Studies have shown that children with Prader-Willi syndrome treated with GH have a decrease in fat mass and an increase in lean body mass, an increase in growth velocity and in resting energy expenditure. It is unknown if treatment of children with Prader-Willi syndrome with GH causes changes in the hypothalamus, or if the effects are peripheral. This study will investigate the benefits of GH on hypothalamic recognition of hunger and satiety, as well as on the basal metabolic rate and body composition of PWS individuals. We will compare the neuroanatomical correlates of hunger and satiation using functional MRI on PWS patients before and one year after GH treatment. In addition, we will use normal weight siblings and non-PWS obese individuals as additional comparison groups. Blood will be drawn to determine various hormonal and neurotransmitter levels at times correlating with hunger and satiety in these individuals. Basal metabolic rate and body composition via dual energy X-ray absorptiometry; will be assessed for all individuals, and will be reevaluated in PWS subjects one year after treatment with GH.