Neuroanatomic Studies in Prader-Willi Syndrome and Early-onset Obesity

描述(由申请人提供)： 儿童肥胖症是一种世界性流行病，影响着年龄越来越小的儿童。在这个项目中，我们将对肥胖的遗传来源明确的儿童和来源不明的肥胖儿童进行比较，以检验肥胖本身不受遗传机制影响的假设。Prader-Willi综合征(PWS)是一种连续的基因缺陷，导致早发性儿童肥胖症的明确模式。环境干预(即父母的警觉)可以显著降低PWS的肥胖程度，并潜在地保护认知功能。因此，PWS是阐明遗传和肥胖对大脑发育的相对贡献的一个很好的模型。一组患有早发性病态肥胖(EMO)的儿童将作为对照组，进一步评估我们的假设，即肥胖，无论原因如何，都会损害大脑发育。过多的脂肪组织会导致多种激素和细胞因子的异常水平。我们最近发现，与正常体重控制的兄弟姐妹相比，这两组患者(EMO和PWS)的脑白质损伤都出现了过早的发展(Miller等人，2006年)。在这个项目中，我们将对大脑核磁共振进行定性和定量的测量，以比较(1)在童年早期变得肥胖的PWS患者和(2)在儿童早期保持正常体重的PWS患者，(3)EMO儿童，以及(4)两组正常体重的同胞对照，以检验我们的假设，即随着早发性肥胖而出现的激素和代谢环境异常会损害神经发育。在这项资助中，我们正在寻找证据，证明在不同病因和肥胖程度的人群中，早发性肥胖与脑损伤之间存在联系。这项研究将提供关于儿童肥胖可能造成的后果--对发育中的大脑的损害--的宝贵信息。患有肥胖症的儿童只占儿童早期肥胖儿童的一小部分，但这将有助于区分肥胖的影响和遗传的影响，因为患有EMO的群体可能有各种不同的肥胖原因。由于儿童肥胖是一种流行病，这项研究的结果将对肥胖儿童的早期干预具有重要意义。

DESCRIPTION (provided by applicant): Childhood obesity is a worldwide epidemic which is affecting children at increasingly younger ages. In this project we will compare children with a well-defined genetic origin of obesity with those with obesity of unknown origin to test the hypothesis that obesity itself, independent of genetic mechanism, compromises neural development. Prader-Willi syndrome (PWS) is a contiguous gene defect that results in a well-defined pattern of early-onset childhood obesity. Environmental manipulations (i.e. parental vigilance) can markedly reduce the extent of the obesity in PWS, and potentially protect cognitive function. Therefore, PWS is an excellent model for elucidating the relative contributions of genetics and obesity to brain development. A group of children with early-onset morbid obesity of unknown origin (EMO) will serve as a comparison group to further evaluate our hypothesis that obesity, regardless of the etiology, compromises brain development. Excess adipose tissue results in abnormal levels of a variety of hormones and cytokines. We have recently found that individuals in both these groups (EMO and PWS) had premature development of white matter lesions in the brain, in contrast to their normal weight control siblings (Miller et al, 2006). In this project we will perform qualitative and quantitative measurements of brain MRIs to compare (1) individuals with PWS who become obese early in childhood with (2) individuals with PWS who remain normal weight during early childhood, and (3) children with EMO, and (4) normal weight sibling controls from both groups to test our hypothesis that the abnormal hormonal and metabolic milieu present with early-onset obesity compromises neural development. In this grant we are seeking evidence of a connection between early-onset obesity and brain damage in groups with a different etiology and degree of obesity. This study will provide invaluable information regarding a possible consequence of childhood obesity - damage to the developing brain. Individuals with PWS represent a small fraction of children with early childhood obesity, but will help differentiate the effects of obesity from the effects of genetics, as the group with EMO likely have [sic] a variety of different etiologies for becoming obese. As childhood obesity is an epidemic, the results of this study will have important implications regarding early intervention for children with obesity.