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The NuGO proof of principle study package: a collaborative research effort of the European Nutrigenomics Organisation

机译：NuGO原理证明研究包：欧洲营养基因组学组织的合作研究

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The European Nutrigenomics Organisation (NuGO; www.nugo.org) was established in 2004 and is funded within the Sixth Framework Programme of the European Commission as a network of excellence [4]. The core partners forming NuGO are 23 research units based at universities and research centers. The key objectives of NuGO are: (a) the promotion of molecular nutrition research in Europe; (b) the development and promotion of mechanistic research in nutrition, food and health research by application of omics technologies; and (c) to develop joint research programs. The NuGO Proof of Principle Study package (NuGO PPS) started in 2007 and is one of the collaborative research initiatives within NuGO. The main goals of the NuGO PPS are to: (a) assess the advantages and the limitations of omics applications in nutritional studies; (b) prove that systems biology approaches can provide a better description of the health/disease status of an organism; (c) prove NuGO’s ability as a network of excellence to analyze complex data sets obtained from a federated series of studies, performed at many partner sites, analyzed in different omics platforms in combination with statistics and bioinformatics in an integrative way; and finally (d) optimize the convergence in data sharing by implementing a data integration platform.;The experimental research platform is based on three mouse feeding trials, PPS1, PPS2, PPS3, and a human volunteer trial referred to as the human PPS (both animal and human studies are approved by their respective local ethics committees). All studies are based on an energy challenge and the acute and chronic effects on substrate oxidation and inflammation status in addition to the long term alterations and stability of energy homeostasis. The mouse studies address the effects of time (PPS1) or metabolic challenges (PPS2) or dietary fat content (PPS3) on the development of insulin resistance and the metabolic consequences which are assessed by comprehensive phenotyping. Analysis takes into account the type of diet, the time-dependency of changes and organ-specificity of effects well as the ability of an organism to cope with metabolic dietary stress (bolus of glucose). The human study is designed to assess the biological intra- and inter-individual variation of a huge spectrum of molecular, metabolic and clinical parameters employing the different omics technologies and to assess the scale and patterns of alterations elicited by a simple nutritional intervention—a 36?h fasting period.;The ApoE*3Leiden transgenic mouse is highly susceptible to diet-induced hyperlipoproteinemia and has been established as a valid murine atherosclerosis models mimicking many hallmarks of human metabolism related to diabetes and atherosclerosis [8].In ApoE*3Leiden transgenic mice, the lipid metabolism is humanized (i.e., a more human-like lipoprotein profile). These humanized mice also can serve as a model of insulin resistance. The mouse study was designed and executed by T.K. and R.K., at TNO-Leiden (The Netherlands) including microarray analysis of organs relevant for insulin resistance (liver, adipose tissue, muscle). Parts of the study were donated to NuGO and biosamples are being further analyzed within the NuGO PPS1 research community. The prime goal of the study is to monitor, with high time-resolution, the development of diet-induced obesity (DIO) and insulin resistance. To do so, genome-wide transcriptomic datasets for the course of the development of insulin resistance in liver, white adipose tissue and muscle were generated. Within PPS1, the development of hepatic steatosis is analyzed which includes the development of a (subacute) inflammatory response. Insulin resistance was achieved in the ApoE*3Leiden mice by feeding animals a diet based on 45% fat by energy (beef tallow) over 12?weeks. Insulin resistance was established in the animals by performing a glucose tolerance test 3 day prior to sacrifice (and parallel hyperinsulinemic-euglyc
机译：欧洲营养基因组学组织（NuGO; www.nugo.org）成立于2004年，由欧盟委员会第六框架计划资助，作为一个卓越网络[4]。组成NuGO的核心合作伙伴是位于大学和研究中心的23个研究单位。 NuGO的主要目标是：（a）在欧洲促进分子营养研究; （b）通过应用组学技术发展和促进营养，食品和健康研究的机理研究; （c）制定联合研究计划。 NuGO原理证明研究包（NuGO PPS）于2007年启动，是NuGO内部的合作研究计划之一。 NuGO PPS的主要目标是：（a）评估组学应用在营养研究中的优势和局限性; （b）证明系统生物学方法可以更好地描述生物的健康/疾病状况; （c）证明NuGO作为卓越网络的能力，能够分析从联合研究中获得的复杂数据集，这些研究是在许多合作伙伴站点进行的，并在不同的组学平台中结合统计和生物信息学进行综合分析; （d）通过实现数据集成平台来优化数据共享的融合。;实验研究平台基于三个小鼠喂养试验PPS1，PPS2，PPS3和一个称为人类PPS的人类志愿者试验（两者均动物和人类研究均已获得各自地方伦理委员会的批准。所有研究均基于能量挑战以及能量稳态的长期改变和稳定性，以及对底物氧化和炎症状态的急性和慢性影响。小鼠研究探讨了时间（PPS1）或代谢挑战（PPS2）或饮食脂肪含量（PPS3）对胰岛素抵抗发展和代谢后果的影响，这些影响通过综合表型评估。分析考虑了饮食类型，变化的时间依赖性和影响的器官特异性以及生物体应对代谢性饮食压力（葡萄糖摄入）的能力。这项人体研究旨在通过使用不同的组学技术来评估各种分子，代谢和临床参数在生物学上的个体内和个体间变异，并通过简单的营养干预来评估改变的规模和模式（36）。禁食期; ApoE * 3Leiden转基因小鼠对饮食诱导的高脂蛋白血症高度敏感，已被确立为有效的鼠类动脉粥样硬化模型，模仿了许多与糖尿病和动脉粥样硬化有关的人类代谢特征[8]。在小鼠中，脂质代谢是人源化的（即更像人的脂蛋白谱）。这些人源化的小鼠也可以作为胰岛素抵抗的模型。鼠标研究是由T.K.设计并执行的。和R.K.，位于TNO-Leiden（荷兰），包括与胰岛素抵抗相关的器官（肝脏，脂肪组织，肌肉）的微阵列分析。研究的一部分捐赠给了NuGO，生物样品正在NuGO PPS1研究社区中进一步分析。这项研究的主要目标是以高时间分辨率监测饮食引起的肥胖症（DIO）和胰岛素抵抗的发展。为此，生成了在肝脏，白色脂肪组织和肌肉中胰岛素抵抗发展过程的全基因组转录组数据集。在PPS1中，分析了肝脂肪变性的发展，其中包括（亚急性）炎症反应的发展。在ApoE * 3Leiden小鼠中，通过在12周内以能量（牛脂）为基础给动物喂食基于45％脂肪的饮食，实现了胰岛素抵抗。通过在处死前3天进行葡萄糖耐量试验，在动物中建立胰岛素抵抗（和平行的高胰岛素-正常血糖）

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