PREDICTIVE TOOL FOR METABOLIC DEVELOPMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：生成代谢综合征风险增加的早期诊断，以便于干预和预防性治疗，并为疾病的机制基础提供见解。 代谢综合征会改变影响新陈代谢和炎症的血清因素，包括脂蛋白、脂肪酸和脂肪因子。我们将使用恒河猴模型来确定这些因子在发病前状态的水平是否可以预测未来的疾病发展。这项研究将检验脂蛋白、脂肪酸和脂肪因子促炎症特征相结合，构成代谢综合征发展的早期预测因子的假设。 目的：测定诊断时和发病前2年健康对照和受损动物血清中脂蛋白颗粒的分布情况。 具体目标2：量化健康和受损动物发病前后血清中的脂肪酸浓度和组成。 具体目的3：测定发病前后健康和受损动物血清中脂肪因子和促炎性因子的水平。 这项研究是新颖的，因为它探索了血清脂肪因子和血脂谱作为代谢综合征风险增加的预测标志的联合使用。这项研究背后的理论基础是，新陈代谢和炎症是通过两个过程共同的血清因素联系在一起的。由于这些因素可能导致代谢综合征风险的增加，因此在确定关键因素后，可能会阐明新的治疗策略。该项目意义重大，因为它有可能提供关键的早期诊断，这将极大地改善有代谢综合征发展风险的肥胖儿童患者的预后。 这项研究才刚刚开始，因此尚未产生数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To generate early warning diagnostics for increased metabolic syndrome risk that will facilitate intervention andpreventative treatment, and provide insights into the mechanistic basis of the disease. Metabolic syndrome alters serum factors that influence metabolism and inflammation, including lipoproteins, fatty acids and adipokines. We will use the rhesus macaque model to determine whether levels of these factors in the pre-diseased state can be predictive of future disease development. This study will test the hypothesis that lipoprotein, fatty acid, and adipokine pro-inflammatory profiles, in combination, constitute an early predictor of metabolic syndrome development. Specific Aim1: To determine the lipoprotein particle size distribution profile in serum from healthy controls and impaired animals at the time of diagnosis and 2 years before disease onset. Specific Aim 2: To quantify fatty acid concentration and composition in serum from healthy and impaired animals before and after disease onset. Specific Aim 3: To determine levels of adipokines and pro-inflammatory factors in serum from healthy and impaired animals before and after disease onset. This study is novel in that it explores the use of serum adipokine and lipid profiles in combination as a predictive marker of increased risk for metabolic syndrome. The rationale behind this study is that metabolism and inflammation are linked through serum factors common to both processes. Because these elements are likely responsible for increased risk for metabolic syndrome, novel therapeutic strategies may be elucidated upon identification of the key factors. The project is significant in that it has the potential to provide a critical early diagnostic that would dramatically improve outcomes for obese pediatric patients that are at risk of metabolic syndrome development. The study has only begun and as such data have yet to be generated.