IDENTIFYING GENES FOR OBESITY QTLS RELATED TO CVD

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 脂肪组织在维持与脂肪和葡萄糖代谢相关的正常生理功能方面发挥着重要作用，因此这些功能的破坏会增加心血管疾病和2型糖尿病的风险。脂肪组织调节个体患心血管疾病和糖尿病风险的机制尚不清楚。然而，最近的研究结果表明，脂肪组织是一个活跃的内分泌器官，能产生许多蛋白质。这些蛋白质对多种代谢途径有很强的作用，尤其是对脂肪和血糖的调节有很大的影响。此外，越来越多的证据表明，饮食结构，特别是脂肪和胆固醇的含量，可以对许多参与代谢过程的基因的表达产生重大影响，包括那些与脂肪组织功能相关的基因。作为当前研究的一部分，我们现在已经开始识别具有显著影响的数量性状基因座(QTL 关于脂肪组织功能的调节，并评估其对心血管疾病和2型糖尿病的影响。我们建议研究显著QTL的特定位置候选基因对与肥胖和脂肪组织内分泌功能相关的表型的影响。我们将进一步评估 通过使用来自大规模人类心血管遗传学研究的高密度SNP数据进行复制分析，检测到的狒狒候选基因关联与人类的相关性。我们还建议研究慢性高胆固醇、高脂肪饮食挑战对脂肪组织组成和功能的影响，并确定脂肪组织特征的变化如何与心血管疾病和糖尿病风险曲线的变化相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Adipose tissue plays an important role in maintaining normal physiological functions associated with lipid and glucose metabolism such that the disruption of these functions leads to increasing risks for both cardiovascular disease and type 2 diabetes. The mechanisms by which adipose tissue mediates an individual's risk of developing cardiovascular disease and diabetes are not clearly understood. However, results of recent studies have demonstrated that adipose tissue is an active endocrine organ producing a number of proteins. These proteins have potent effects on a variety of metabolic pathways and in particular appear to exert a significant effect on lipid and glucose regulation. In addition, there is growing evidence that dietary make-up, particularly the fat and cholesterol content, can have significant effects on the expression of many genes involved in metabolic processes including those associated with adipose tissue function. As part of the current study, we have now begun to identify quantitative trait loci (QTLs) with significant effects on the regulation of adipose tissue function and to assess their impact on cardiovascular disease and type 2 diabetes. We propose to examine the effects of specific positional candidate genes for significant QTLs on phenotypes related to adiposity and adipose tissue endocrine function. We will evaluate further the relevance for humans of detected candidate gene associations in the baboon by conducting replication analyses using high density SNP data from a large-scale human cardiovascular genetics study. We also propose to examine the effects of a chronic high cholesterol, high fat dietary challenge on the composition and function of adipose tissue and to determine how changes in the characteristics of adipose tissue relate to changing risk profiles for cardiovascular disease and diabetes.