Serum Metabolomic/Proteomic Profiles in CALERIE

CALERIE 中的血清代谢组学/蛋白质组学分析

• 批准号: 7102005
• 负责人: BRUCE S KRISTAL
• 金额: $ 37.82万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-03-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102005
• 关键词: blood chemistry; breast neoplasms; caloric dietary content; cancer risk; clinical research; diabetes risk; dietary restriction; geographic difference; human subject; information systems; mathematical model; metabolomics; model design /development; noninsulin dependent diabetes mellitus; patient /disease registry; phlebotomy; plasma; proteomics; serum

DESCRIPTION (provided by applicant): Calorie Restriction (CR) is the most potent, robust, and reproducible known means of extending longevity and decreasing morbidity in lab rodents. Despite 70 years of research, the relevance of this observation for humans remains unknown. Relevance is supported by the established link between obesity and morbidity in humans. Potential linkages are being directly addressed by the NIH-sponsored CALERIE (comprehensive assessment of long-term effects of reducing intake of energy) study. This study will enroll approximately 250 individuals and collect blood samples at 6 time points over 24 months. Our proposed ancillary study has two goals: (A) to support CALERIE by characterizing the plasma metabolome and proteome in these samples; the initial foci being to determine if pre-existing metabolomic profiles, and proteomic profiles being developed in NIH funded studies, enable us to follow CR in people from three geographically distinct sites (thus linking human studies to the rodent literature) and to identify metabolites and pathways of interest, and; (B) to provide data grounding and linking the PI's ongoing studies of the use of metabolomic and proteomic profiles from CR rats to predict future disease risk for type II diabetes and breast cancer with direct data on human caloric intake. Multivariate pattern recognition analysis based on a 93 metabolite profile can distinguish ad libitum fed (AL) and CR rats (100% accuracy in training sets, mean >90% in test sets), and has enabled construction of accurate models of intermediate intakes (r2=0.88) for individual rats. Analytical work has adapted this profile for human plasma. Initial sera proteome profiles also distinguish diet with 100% accuracy. The AIMs are: (1) To determine temporal shifts that occur in the proteome and metabolome at the levels of compounds, pathways, and profiles. Then to use these data to (a) determine quantitative fit to a CR profile pre-, during, and, if possible, post- intervention, and; (b) quantitatively assess movement along a mathematical continuum related to progressive CR in rats. (2) To provide an electronic archive of the metabolomic and proteomic constituents of the blood of participants that could be repeatedly mined for future testing of new hypotheses; (3) To develop mathematical models sensitive to short and long-term low calorie diets in humans to be used in complement with models of disease prediction now being generated in the PIs lab, and; (4) To examine profile changes across the three CALERIE sites to compare and contrast observed changes.

描述（由申请人提供）： 卡路里限制（CR）是延长寿命和降低实验室啮齿动物发病率的最有效，最强大且可再现的已知手段。尽管进行了70年的研究，但这种观察与人类的相关性仍然未知。相关性得到了肥胖与人类发病率之间的既定联系的支持。 NIH赞助的热量（对减少能源摄入的长期影响的全面评估）直接解决了潜在的联系。这项研究将招募约250个人，并在24个月内在6个时间点收集血液样本。我们提出的辅助研究有两个目标：（a）通过表征这些样品中的血浆代谢组和蛋白质组来支持卡列利；最初的焦点是确定在NIH资助的研究中开发的先前存在的代谢概况以及蛋白质组学特征，使我们能够跟随来自三个地理位置上不同地点（从而将人类研究与啮齿动物文献联系起来）的人的CR，并识别出感兴趣的代谢物和途径，以及； （b）提供数据接地，并将PI的持续研究与CR大鼠的代谢组和蛋白质组学特征的使用相关联，以预测II型糖尿病和乳腺癌的未来疾病风险，并直接数据与人类热量摄入有关。基于93个代谢物谱的多元模式识别分析可以区分自由饲料（AL）和CR大鼠（训练集的100％精度，平均值> 90％），并且可以为单个大鼠构建准确的中间摄入量模型（R2 = 0.88）。分析工作已将此概况适应人类血浆。最初的血清蛋白质组曲线还以100％的精度区分饮食。目的是：（1）确定在化合物，途径和剖面水平上发生的蛋白质组和代谢组中发生的时间变化。然后，将这些数据用于（a）确定对CR轮廓前，期间和（如果可能的）进行定量拟合，并在干预后； （b）定量评估与大鼠进行性CR相关的数学连续性运动。 （2）提供参与者血液代谢组和蛋白质组学成分的电子档案，可以反复开采以将来进行新假设的未来测试； （3）开发对人类短期和长期低卡路里饮食敏感的数学模型，以与现在在PIS实验室中产生的疾病预测模型相辅相成，并且； （4）检查三个热量位点之间的轮廓变化以比较和对比观察到的变化。