High Resolution Plasma Lipidomics in CALERIE

CALERIE 中的高分辨率血浆脂质组学

• 批准号: 8716633
• 负责人: BRUCE S KRISTAL
• 金额: $ 17.69万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8716633
• 关键词: Address; Ancillary Study; Animals; Back; Biological; Biological Markers; Blood; Blood specimen; Caloric Restriction; Data; Data Set; Databases; Detection; Diet; Disease; Early Intervention; Energy Intake; Enrollment; Epidemiologic Studies; Fatty acid glycerol esters; Future; Genetic; Goals; Health; Human; Individual; Insulin Resistance; Intake; Link; Lipids; Longevity; Malnutrition; Mammals; Measures; Methods; Modeling; Morbidity - disease rate; Obesity; Pattern; Plasma; Population Study; Protocols documentation; Rattus; Research; Resolution; Risk; Rodent; Sampling; Series; Shotguns; Signal Transduction; Site; Staging; Time; Triglycerides; United States National Institutes of Health; base; blood lipid; cohort; design; diabetes risk; disorder risk; feeding; liquid chromatography mass spectrometry; malignant breast neoplasm; metabolomics

DESCRIPTION (provided by applicant): Caloric 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 study. This study has enrolled ~220 individuals and collected blood samples at 6 time points over 24 months. Our proposed ancillary study has two goals: (A) to support CALERIE by characterizing the plasma lipidome in these samples by using a newly developed, high resolution liquid chromatography-mass spectrometry-based profiling approach that enables both qualitative and quantitative detection of >425 structurally identified individual lipids in biological samples (e.g, >100 unique triglycerides), and; (ii) to link these data with our existing metabolomics profiling data within the CALERIE cohort and with an equivalent study in rats fed ad libitum or with a series of diets varying in the extent and duration of caloric restriction. The long-range goals of these latter studies are to develop diet-based biomarkers that have utility in human epidemiological studies (for objective recognition of diet) and which predict disease risk in humans (e.g., breast cancer). In support of this proposal, we have shown that CR induces changes in blood lipids in rats, e.g., a reduction in overall circulating triglycerides. Our finer resolution enables us to also show that there are multiple lipid species specific changes, and that these changes differ in both direction and magnitude, even within a single class of lipids such as triglycerides. Furthermore, we have conducted a pilot lipidomics study of ~400 samples drawn from CALERIE, and we show that the signal we can follow is so strong that, even unblinded (and thus including mixed controls and restricted, at a 1:2 ratio), we are able to show the effect on blood lipids with the CALERIE protocol, and we are able to show similar changes in rats and humans. We hypothesize that the proposed high resolution lipidomics study will reveal additional benefits of low calorie diets in humans. The Aims are: Aim 1: To develop, optimize, and validate a defined series of nested plasma lipidomics-based biomarker profiles Aim 2: To determine the similarities, differences, and interactions between the systemic lipidomics profiles and systemic metabolomics patterns Aim 3: To determine the similarities, differences, and interactions between the systemic lipidomics profiles in humans and those in CR animals The proposed study furthers NIH goals of focusing on health and early interventions rather than late stage disease, and is well within our lab's capacity to complete in 2 years.

描述（由申请人提供）：热量限制（CR）是延长寿命和降低实验室啮齿动物发病率的最有效，可重现的已知手段。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Calerie研究正在直接解决潜在的联系。这项研究已在24个月内招募了约220个人，并在6个时间点收集了血液样本。我们提出的辅助研究有两个目标：（a）通过使用新开发的，高分辨率的基于基于液态的液态分析方法来表征这些样品中的血浆脂肪组，从而实现定性和定量检测> 425在生物学样品中均可鉴定出> 425个单独的脂质（例如，生物学样品中的单个脂质（例如） （ii）将这些数据与我们现有的代谢组学分析数据联系起来，并在热量限制的程度和持续时间内对大鼠或一系列饮食的大鼠进行了同等研究。这些后者研究的远程目标是开发基于饮食的生物标志物，这些生物标志物在人类流行病学研究（用于饮食的客观识别）中，并预测人类疾病的风险（例如乳腺癌）。为了支持该提案，我们已经表明CR诱导大鼠血脂的变化，例如，总循环甘油三酸酯的降低。我们的精细分辨率使我们还可以表明存在多种脂质物种的特定变化，并且这些变化在方向和幅度上也有所不同，即使在一类脂质（例如甘油三酸酯）中也是如此。此外，我们已经对Calerie绘制的〜400个样本进行了试验性脂质组学研究，我们表明我们可以遵循的信号是如此强烈，甚至没有盲目（因此，甚至以1：2的比例包括混合控制和受限），我们能够显示出对Calerie Protoct的效果，并且能够显示出Calerie Protoct的影响，并且我们能够显示出类似的变化。我们假设拟议的高分辨率脂肪态学研究将揭示人类低卡路里饮食的其他好处。 The Aims are: Aim 1: To develop, optimize, and validate a defined series of nested plasma lipidomics-based biomarker profiles Aim 2: To determine the similarities, differences, and interactions between the systemic lipidomics profiles and systemic metabolomics patterns Aim 3: To determine the similarities, differences, and interactions between the systemic lipidomics profiles in humans and those in CR animals The proposed study furthers NIH专注于健康和早期干预而不是晚期疾病的目标，并且符合我们实验室两年内完成的能力。