PAT PROTEINS: GENE-DIET INTERACTIONS OBESITY RISK AND HEALTH

PAT 蛋白质：基因-饮食相互作用肥胖风险与健康

• 批准号: 7342051
• 负责人: Jose M. Ordovas
• 金额: $ 32万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342051
• 关键词: Abdomen; Adipocytes; Adipose tissue; Adult; Affect; Age; Aging; Alleles; American; Amino Acid Sequence; Animals; Asians; Binding Proteins; Biochemical; Body Weight; Body Weight Changes; Body Weight decreased; Body fat; Body mass index; Body measure procedure; Calories; Candidate Disease Gene; Central obesity; Characteristics; Chinese People; Classification; Clinical; Complex; Condition; Conjugated Linoleic Acids; Coronary heart disease; Cultural Backgrounds; Data; Development; Diet; Diet Habits; Dietary Component; Dietary Factors; Dietary Fats; Dietary intake; Disease; Dual-Energy X-Ray Absorptiometry; Eating; End Point; Energy Intake; Energy Metabolism; Epidemic; Equilibrium; Ethnic group; Exercise; Family; Family member; Fatty acid glycerol esters; Female; Framingham Heart Study; Gender; Gene Family; Gene Proteins; Genes; Genetic; Genetic Markers; Genotype; Haplotypes; Health; Heritability; Hip region structure; Human; In Vitro; Individual; Insulin Resistance; Intake; Life; Life Style; Light; Lipids; Lipolysis; Measures; Menopausal Status; Metabolic Pathway; Metabolic syndrome; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Observational Study; Overweight; PPAR gamma; Participant; Peptide Sequence Determination; Personal Satisfaction; Phenotype; Play; Population; Population Study; Prevention therapy; Proteins; Public Health; Range; Recommendation; Regulation; Research; Research Personnel; Risk; Rodent; Role; Singapore; Single Nucleotide Polymorphism; Societies; Spain; Testosterone; Thinking; Time; Today; Translating; United States; Variant; Visceral; Weight; Woman; Work; X-Ray Computed Tomography; adipophilin; age related; base; clinically relevant; experience; falls; fighting; gain of function; gene interaction; genetic association; genetic variant; interest; lipid biosynthesis; loss of function; mannose 6 phosphate; member; men; mortality; neglect; obesity prevention; obesity risk; perilipin; programs; receptor binding; sedentary; size; sterol esterase; success; trait; waist circumference

DESCRIPTION (provided by applicant): Obesity has been identified as "one of today's most blatantly visible - yet most neglected - public health problems." Like most disorders affecting the well-being of the population at-large, obesity is a complex condition in which multiple determinants interact to produce the undesired end-point. More than 1.1 billion people worldwide fall within the classification of overweight or obese. How and why did the world get so fat? The global answer may be simple: Too many calories and too little exercise. However, at the individual level the answer is more complex as shown by the very limited long term success achieved by weight-reducing therapies. We know that at the individual level obesity is determined by a combination of environmental and genetic factors. The heritability of obesity is estimated to range from 0.37 to 0.52. However, much less is known about the precise contribution of specific genes to the current obesity epidemic. Although hundreds of obesity candidate genes have been identified through different metabolic pathways, the fundamental basis of obesity resides with excessive storage of triacylglycerides (TAG) in adipose tissue. The mechanisms that control the storage and release of TAG in lipid droplets are complex and poorly understood; yet, they are likely to be crucial to the understanding of the regulation of energy metabolism and body weight. In this regard, the evolutionarily related family of PAT proteins (Perilipin (PLIN), Adipophilin, TIP47, S3-12) defined by protein sequence similarity and their association with lipid droplets, may play key roles in obesity. We have recently shown that common variants at the PLIN locus were associated with BMI and obesity risk in females from several large population studies, including Whites, Chinese, Indians and Malays. However, nothing is known about the contributions of other PAT genes to obesity. Moreover, information is lacking about the role that PAT genes may play on the longitudinal changes in BMI that take place in modern societies during aging. Finally, the potential interactions between these genes and dietary factors may shed light on the complex relation between dietary intake and body weight changes observed on an individual basis. Therefore, the primary objective of this application is to identify common genetic variants of the PAT family of genes and to relate those variants with anthropometric measures (BMI, waist circumference, visceral and total body fat) and their changes over time in -2600 men and women from the Framingham Heart Study, using the wealth of cross-sectional and longitudinal data available in this study. Moreover, we will evaluate interactions between genetic variants and dietary habits as modulators of obesity and related anthropometric measures. This research has the potential of translating findings of genetic associations and interactions into dietary recommendations for specific groups selected according to their genetic characteristics in order to increase the success of dietary measures aimed to fight the obesity epidemic.

描述（由申请人提供）：肥胖已被确定为“当今最公然可见的（但最被忽视）的公共卫生问题之一。像大多数影响总体人口福祉的疾病一样，肥胖是一种复杂的疾病，其中多种决定因素相互作用以产生不希望的终点。全球超过11亿人属于超重或肥胖的分类。世界如何以及为什么变得如此胖？全球答案可能很简单：卡路里太多，运动太少。但是，在个人层面上，答案更为复杂，如减轻体重疗法所获得的长期成功所表明的那样。我们知道，在个人一级，肥胖是由环境和遗传因素的结合决定的。肥胖的遗传力估计为0.37至0.52。但是，关于特定基因对当前肥胖流行的精确贡献的知之甚少。尽管已经通过不同的代谢途径鉴定出数百种肥胖候选基因，但肥胖的基本基础却属于脂肪组织中三酰基甘油酸酯（TAG）的过量储存。控制脂质液滴中标签的存储和释放的机制很复杂且理解较低。但是，它们可能对理解能量代谢和体重的调节至关重要。在这方面，由蛋白质序列相似性及其与脂质液滴的关联定义的PAT蛋白（Perilipin（Plin），脂肪蛋白，TIP47，S3-12）的进化相关的家族可能在肥胖症中起关键作用。我们最近表明，PLIN基因座的常见变体与来自白人，中国人，印第安人和马来人在内的几项大型人群研究的女性中的BMI和肥胖风险有关。但是，对其他PAT基因对肥胖的贡献一无所知。此外，关于PAT基因在衰老期间现代社会发生的BMI纵向变化中可能扮演的角色的信息。最后，这些基因与饮食因素之间的潜在相互作用可能会揭示饮食摄入量与体重变化之间的复杂关系。因此，本应用的主要目的是确定PAT基因家族的常见遗传变异，并将这些变体与人体测量指标（BMI，腰围，内脏和全身脂肪）及其随时间的变化相关联-2600名男性和随时间的变化来自弗雷明汉心脏研究的妇女使用本研究中可用的横断面和纵向数据的财富。此外，我们将评估遗传变异和饮食习惯之间的相互作用，作为肥胖和相关人体测量指标的调节剂。这项研究的潜力将遗传关联和相互作用的发现转化为根据其遗传特征选择的特定组的饮食建议，以增加旨在与肥胖症患者作斗争的饮食措施的成功。