Adiposity, Disease Risk Factors, and Lifetime Health

说明(申请人提供)：超重/肥胖、代谢紊乱的发展及其相互关系的性质在整个生命周期内，从儿童早期到成年，是一个对公共卫生有巨大影响的问题。内脏肥胖通过其与血管炎症、激素紊乱和胰岛素抵抗的代谢相关，在许多慢性疾病的病因中发挥着独特的作用。最近的研究表明，内脏脂肪堆积和肝脏脂肪沉积增加之间存在潜在的机制联系。肝脏脂肪堆积增加可能导致胰岛素抵抗、血脂异常，以及心血管疾病和2型糖尿病的风险。然而，目前对正常健康个体肝脏脂肪积累的自然过程知之甚少。这项拟议的研究将使用来自FELS纵向研究的新数据和现有数据，这是一个始于1929年的独特数据库。FELS纵向研究是世界上最长的关于随机确定的个人的生长、身体成分和慢性病风险因素的连续研究。这一延续建议的一个主要焦点是全面评估脂肪组织在心脏代谢性疾病风险中的作用。几个仓库中的肝脏脂肪含量和腹部脂肪组织将通过磁共振成像(MRI)进行量化，以检查肝脏脂肪、内脏和皮下脂肪以及全身脂肪与心脏代谢性疾病风险之间的相互关系。这些数据将与现有数据相结合，通过进行系列和横断面分析来检验各种假设。拟议的继续研究有四个具体目标：1)阐明肝脏脂肪和腹部脂肪组织(内脏、浅层和深层皮下)在FELS纵向研究参与者中积累的决定因素；2)阐明不同脂肪组织之间的联系和潜在的机制途径，包括肝脏、腹部(内脏、浅层和深层皮下)和全身；3)阐明不同脂肪组织库(包括肝脏、腹部和全身)与心脏代谢风险的关系；4)使用长期系列数据阐明儿童和成年期间身体成分变化模式、传统心血管疾病和T2 DM危险因素、全身炎症因素和脂肪细胞因子之间的关系。根据这一竞争性更新建议收集的数据将提供更好和更完整的了解不同脂肪组织之间的生理关系和心脏代谢疾病的风险，如非酒精性脂肪性肝病、心血管疾病和T2 DM。 与公共健康相关：超重/肥胖的发展在美国是一个具有巨大公共健康影响的问题。这项拟议的研究使用了FELS纵向研究的数据，这是一个始于1929年的独特数据库，以检查肥胖、肝脏脂肪堆积和慢性病风险之间的相互关系。

DESCRIPTION (provided by applicant): The development of overweight/obesity, metabolic disorders, and the nature of their interrelationships over the lifespan, from early childhood throughout adulthood, is a problem with immense public health implications. Visceral obesity, through its metabolic association with vascular inflammation, hormonal disturbances, and insulin resistance, plays a unique role in the etiology of many chronic diseases. Recent studies have demonstrated potential mechanistic links between visceral fat accumulation and increased deposition of fat in the liver. Increased fat accumulation in the liver may lead to insulin resistance, dyslipidemia, and risk for CVD and T2DM. However, little is currently known about the natural progression of liver fat accumulation in normal healthy individuals. This proposed research will use both new and existing data from the Fels Longitudinal Study, a unique database that began in 1929. The Fels Longitudinal Study is the world's longest continuous serial study of growth, body composition and risk factors for chronic disease in randomly ascertained individuals. A major focus of this continuation proposal is the comprehensive assessment of the role of adipose tissue in cardiometabolic disease risk. Liver fat content and abdominal adipose tissue in several depots will be quantified by magnetic resonance imaging (MRI) in order to examine the interrelationships among liver fat, visceral and subcutaneous abdominal adiposity, and total body adiposity with respect to risk for cardiometabolic diseases. These data will be combined with existing data to test a variety of hypotheses by conducting both serial and cross-sectional analyses. There are four specific aims to the proposed continuation: 1) Elucidate the determinants of liver fat and abdominal adipose tissue (visceral, superficial and deep subcutaneous) accrual in Fels Longitudinal Study participants; 2) Elucidate associations and potential mechanistic pathways among different adipose tissue depots including the liver, abdomen (visceral, superficial and deep subcutaneous) and total body; 3) Elucidate relationships among different adipose tissue depots (including the liver, abdomen, and total body) and cardiometabolic risk; and 4) Elucidate relationships among patterns of change in body composition, traditional CVD and T2DM risk factors, systemic inflammatory factors, and adipocytokines during childhood and adulthood using long-term serial data. The data collected under this competitive renewal proposal will provide a better and more complete understanding of the physiological relationships among different adipose tissue depots and risk for cardiometabolic diseases such as non- alcoholic fatty liver disease, CVD, and T2DM. PUBLIC HEALTH RELEVANCE: The development of overweight/obesity is a problem in the United States with immense public health implications. This proposed research uses data from the Fels Longitudinal Study, a unique database that began in 1929, to examine the inter-relationships between obesity, liver fat accrual and chronic disease risk.