Metabolomics Profiling of Biological Responses to Changes in Air Pollution Levels

对空气污染水平变化的生物反应的代谢组学分析

基本信息

批准号：
9298659
负责人：
Lina Mu
金额：
$ 19.28万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9298659
关键词：
Address Adult Air Air Pollutants Air Pollution Alpha Cell Biological Biological Assay Biological Markers Cardiovascular Diseases Cell physiology Clinical Collection Congenital Abnormality Data Detection Disease Early Diagnosis Eicosanoids Enrollment Ensure Environmental Exposure Environmental Pollutants Epidemiology Evaluation Exposure to Fatty Acids Female Future Gene Expression Gene Proteins Generations Health Human Hypersensitivity Inflammation Inflammatory Inflammatory Response Intervention Investigation Link Lipid Peroxidation Lipid Peroxides Malignant Neoplasms Measures Mediator of activation protein Metabolic Mission Molecular Weight National Institute of Environmental Health Sciences Nature Organ Organism Outcome Oxidative Stress Parents Participant Pathogenesis Pathogenicity Pathway Analysis Pathway interactions Pharmacotherapy Pilot Projects Process Production Reporter Research Research Design Risk Role Sampling Serum Specimen Sputum Stress Time Tissues United States National Institutes of Health Urine Validation air pollution control design environmental stressor epidemiology study exposed human population glutathione peroxidase insight interest lipid mediator male metabolic profile metabolome metabolomics neurodevelopment non-smoking novel outcome forecast response tool

项目摘要

Abstract The metabolome represents the collection of the end products of cellular processes, and is the most proximal reporter of the body's response to environmental exposure, disease processes, and drug therapy. Metabolomics has been put forward as a powerful tool for studying various clinical outcomes, including diseases related to air pollution exposure, such as cancer and cardiovascular diseases. So far, application of metabolomics to studying air pollution related mechanisms has been very limited. We hypothesize that changes in air pollution levels are associated with metabolic changes in multiple pathways, including inflammation and oxidative stress. Metabolomics, owing to its comprehensive and unbiased nature of analysis, has the advantage of discovering new biomarkers and revealing novel mechanisms. The Beijng Olympics Air Pollution Study is a panel study we conducted during Beijing Olympics when temporary air pollution control measures were implemented. The study enrolled 201 adults prior to Beijing's air quality improvement initiative and followed them to investigate the short-term effects of air pollution exposure in humans. Biological specimens were collected and banked from each participant at baseline, during, and after the Olympics. Utilizing stored serum samples from a subset (66 participants) of this existing study, we propose (1) to conduct a targeted assay on the metabolic profile of lipid peroxidation and inflammatory lipid mediators (13 metabolites) to examine metabolic responses to the changes in air pollution levels over the three study periods, and (2) to conduct a untargeted analysis using a high throughput approach (886 metabolites) to discover the metabolites that respond strongly to drastic changes in air pollution levels, as well as to identify novel pathways and metabolic signatures that represent overall metabolic changes. We have conducted a pilot study to explore the feasibility of the proposed project. We observed obvious changes in multiple pathways, including fatty acid lipid peroxides and eicosanoids, which are consistent with the results from our parent study in which glutathione peroxidase (GPx) activities were induced by air pollution exposure. We anticipate that the proposed study will provide an example of using metabolomics to study human exposure to air pollution, reveal the critical role of lipid peroxidation and inflammatory lipid mediators, and generate novel hypotheses regarding relevant pathways for future study. The profile exploration may advance our current understanding of overall human biological responses to air pollution exposure. We anticipate that these findings will be linked with clinical outcomes in future studies.

抽象的代谢组代表细胞过程最终产物的集合，是最重要的身体对环境暴露、疾病过程和药物治疗的反应的近端报告者。代谢组学已被提出作为研究各种临床结果的强大工具，包括与空气污染暴露有关的疾病，例如癌症和心血管疾病。到目前为止，申请代谢组学在研究空气污染相关机制方面的应用非常有限。我们假设空气污染水平的变化与多种途径的代谢变化有关，包括炎症和氧化应激。代谢组学由于其全面且公正的性质分析，具有发现新生物标志物和揭示新机制的优势。北京奥运会空气污染研究是我们在北京奥运会期间进行的一项面板研究。实施临时大气污染防治措施。该研究在北京之前招募了 201 名成年人空气质量改善倡议并跟踪他们调查空气污染的短期影响暴露于人类。在基线时从每个参与者那里收集并储存生物样本，奥运会期间和之后。利用该子集（66 名参与者）中储存的血清样本现有的研究，我们建议（1）对脂质过氧化的代谢谱进行有针对性的测定，并且炎症脂质介质（13 种代谢物），用于检查对空气变化的代谢反应三个研究期间的污染水平，以及（2）使用高通量方法（886 种代谢物）来发现对剧烈变化有强烈反应的代谢物空气污染水平，以及确定代表整体的新途径和代谢特征代谢变化。我们已进行试点研究，探讨建议项目的可行性。我们观察到明显的多种途径的变化，包括脂肪酸脂质过氧化物和类二十烷酸，这与我们的母研究结果，其中谷胱甘肽过氧化物酶 (GPx) 活性是由空气诱导的污染暴露。我们预计拟议的研究将提供一个使用代谢组学的例子研究人类暴露于空气污染中，揭示脂质过氧化和炎症脂质的关键作用中介者，并就未来研究的相关途径提出新的假设。简介探索可能会增进我们目前对人类对空气污染的整体生物反应的理解接触。我们预计这些发现将与未来研究中的临床结果联系起来。