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

普瑞德威利综合征和早发性肥胖的神经解剖学研究

• 批准号: 8050081
• 负责人: JENNIFER L MILLER
• 金额: $ 17.05万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8050081
• 关键词: 4 year old; Adipose tissue; Affect; Age; Birth; Body mass index; Brain; Brain Injuries; Child; Childhood; Data; Defect; Development; Diffusion Magnetic Resonance Imaging; Early treatment; Enrollment; Epidemic; Etiology; Frequencies; Genes; Genetic; Grant; Growth; Hormonal; Hormones; Incidence; Individual; Lesion; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Methodology; Modeling; Molecular; Morbid Obesity; Obesity; Participant; Pattern; Prader-Willi Syndrome; Prevalence; Recording of previous events; Relative (related person); Research Personnel; Siblings; Techniques; Testing; Time; Training; Weight; Weight maintenance regimen; brain volume; cognitive function; comparison group; cytokine; early childhood; early onset; gray matter; myelination; neurodevelopment; obesity in children; premature; programs; vigilance; white matter

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.

描述（由申请人提供）： 儿童肥胖症是一种世界性流行病，影响儿童的年龄越来越小。在这个项目中，我们将比较具有明确的肥胖遗传起源的儿童与那些具有未知起源的肥胖的儿童，以检验肥胖本身独立于遗传机制而损害神经发育的假设。Prader-Willi综合征（PWS）是一种连续的基因缺陷，导致明确的早发性儿童肥胖模式。环境控制（即父母的警惕性）可以显着降低PWS的肥胖程度，并可能保护认知功能。因此，PWS是一个很好的模型，用于阐明遗传和肥胖对大脑发育的相对贡献。一组患有不明原因早发性病态肥胖（EMO）的儿童将作为对照组，以进一步评估我们的假设，即肥胖，无论病因如何，都会影响大脑发育。过多的脂肪组织导致各种激素和细胞因子的异常水平。我们最近发现，与正常体重对照组的同胞相比，这两组（EMO和PWS）中的个体在大脑中过早出现白色病变（米勒等人，2006）。在这个项目中，我们将进行定性和定量的脑MRI测量，以比较（1）在儿童早期肥胖的PWS患者与（2）在儿童早期保持正常体重的PWS患者，以及（3）EMO儿童，和（4）正常体重的同胞对照，以检验我们的假设，即异常的激素和代谢环境存在早期-开始肥胖会损害神经发育。在这项研究中，我们正在寻找证据，证明早发性肥胖和不同病因和肥胖程度的脑损伤之间的联系。这项研究将提供关于儿童肥胖可能造成的后果--对发育中的大脑造成损害的宝贵信息。PWS个体代表了一小部分早期儿童肥胖儿童，但将有助于区分肥胖的影响与遗传学的影响，因为EMO组可能有各种不同的肥胖病因。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。