Adiposity, Disease Risk Factors, and Lifetime Health

描述（由申请人提供）：超重/肥胖、代谢紊乱的发展，以及它们在整个生命周期（从幼儿到成年）中相互关系的性质，是一个具有巨大公共卫生影响的问题。内脏性肥胖，通过其与血管炎症、激素紊乱和胰岛素抵抗的代谢关联，在许多慢性疾病的病因学中起着独特的作用。最近的研究表明，内脏脂肪积累与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，目前对正常健康人肝脏脂肪堆积的自然过程知之甚少。这项拟议中的研究将使用费尔斯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。费尔斯纵向研究是世界上对随机确定的个体的生长、身体组成和慢性疾病风险因素进行的最长的连续系列研究。这一延续提案的一个主要焦点是全面评估脂肪组织在心脏代谢疾病风险中的作用。几个仓库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、内脏和皮下腹部脂肪以及全身脂肪与心脏代谢疾病风险之间的相互关系。这些数据将与现有数据相结合，通过进行序列和横断面分析来检验各种假设。有四个具体的目标，建议继续：1)阐明肝脏脂肪和腹部脂肪组织（内脏，浅表和深皮下）在费尔斯纵向研究参与者中积累的决定因素；2)阐明肝脏、腹部（内脏、浅表和深皮下）和全身不同脂肪组织库之间的关联和潜在的机制途径；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)利用长期序列数据阐明儿童和成年时期身体组成、传统CVD和T2DM危险因素、全身炎症因子和脂肪细胞因子的变化模式之间的关系。在这项竞争性更新提案下收集的数据将提供更好和更完整的了解不同脂肪组织库与心脏代谢疾病（如非酒精性脂肪性肝病、CVD和T2DM）风险之间的生理关系。

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.