Adiposity, Disease Risk Factors, and Lifetime Health

描述（由申请人提供）：超重/肥胖、代谢紊乱的发展及其在整个生命周期中（从幼儿期到成年期）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，内脏脂肪积累和肝脏脂肪沉积增加之间存在潜在的机械联系。肝脏中脂肪蓄积增加可能导致胰岛素抵抗、血脂异常以及CVD和T2 DM风险。然而，目前对正常健康个体肝脏脂肪积累的自然进展知之甚少。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。Fels纵向研究是世界上最长的连续系列研究，随机确定个体的生长，身体组成和慢性疾病的风险因素。这一延续建议的主要重点是全面评估脂肪组织在心脏代谢疾病风险中的作用。将通过磁共振成像（MRI）对几个仓库中的肝脏脂肪含量和腹部脂肪组织进行定量，以检查肝脏脂肪、内脏和皮下腹部肥胖以及全身肥胖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，通过进行系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）阐明肝脂肪和腹部脂肪组织的决定因素Fels纵向研究参与者的（内脏、浅表和深层皮下）累积; 2）阐明不同脂肪组织库（包括肝脏、腹部）之间的关联和潜在机制途径（内脏、浅表和深层皮下）和全身; 3）阐明不同脂肪组织库之间的关系（包括肝脏、腹部和全身）和心脏代谢风险;和4）阐明身体组成变化模式、传统CVD和T2 DM危险因素、全身炎症因子和脂肪细胞因子在儿童期和成年期使用长期序列数据。根据本竞争性更新提案收集的数据将更好、更完整地了解不同脂肪组织库与心脏代谢疾病（如非酒精性脂肪肝、CVD和T2 DM）风险之间的生理关系。 公共卫生相关性：超重/肥胖的发展是美国的一个问题，对公共卫生有巨大的影响。这项研究使用了Fels纵向研究的数据，这是一个始于1929年的独特数据库，旨在研究肥胖，肝脏脂肪积累和慢性疾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.