Dramatic Improvements to the Doubly Labeled Water Technique by Measurement of 17O

通过测量 17O 显着改进双标记水技术

• 批准号: 8201599
• 负责人: Elena S Berman
• 金额: $ 14.94万
• 依托单位: LOS GATOS RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-10 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8201599
• 关键词: Accounting; Adult; Blood; Businesses; Chronic Disease; Clinical; Conduct Clinical Trials; Consumption; Cost Savings; Dose; Energy Intake; Energy Metabolism; Epidemic; Gold; High Prevalence; Human; Individual; Isotopes; Label; Laboratories; Lasers; Legal patent; Life; Liquid substance; Long-Term Effects; Mass Spectrum Analysis; Measurement; Measures; Memory; Metabolic; Methods; Modeling; Monitor; Obesity; Overweight; Performance; Phase; Plasma; Play; Population Study; Public Health; Research; Research Personnel; Research Project Grants; Risk; Role; Sampling; Signal Transduction; Techniques; Technology; Testing; Time; Uncertainty; Urine; Vacuum; Water; Work; base; cost; design; improved; innovation; instrument; metabolic abnormality assessment; novel; professor; prototype; research study; standard measure; stem

DESCRIPTION (provided by applicant): The high prevalence of obesity in the US is a major public health concern, as overweight and obese individuals are at increased risk for many chronic diseases. Obesity stems from an imbalance between total caloric consumption and total energy expenditure (TEE), therefore accurate measurements of TEE play a pivotal role in understanding and ultimately reversing this epidemic. The gold standard for measuring TEE in free-living individuals is the doubly labeled water (DLW) method. The major limitations of the DLW method include high cost and precision of only 1 5% for individual measurements. In this Small Business Innovative Research (SBIR) project, Los Gatos Research (LGR) will develop, fabricate, and test a novel, laser-based analyzer to dramatically improve DLW measurements of TEE by concurrently measuring 17O/16O to correct for natural isotopic fluctuations in 18O and 2H. The Triple Isotope Water Analyzer (TIWA), which will be based on LGR's patented, laser-based Off-Axis ICOS technology, will be capable of real-time, simultaneous, high-throughput (50 samples/day) monitoring of 2H/1H, 18O/16O, and 17O/16O in H2O from human bodily fluids (e.g., blood, urine, and plasma), with a target accuracy of better than 10.60 for 2H/1H, 10.20 for 18O/16O, and 10.30 for 17O/16O at natural isotopic abundances. For enriched body waters that have been labeled with 2H and 18O, the target accuracy will be comparable to isotope ratio mass spectrometry and better than 11.50 for 2H/1H, 10.50 for 18O/16O. The TIWA will allow quantification of isotopic background fluctuation during measurements of TEE, eliminating the significant "constant background" assumption made during DLW experiments. Measurement of the isotopic background fluctuation will allow for much smaller isotopic doses to be used, substantially reducing the cost of TEE measurements. Alternatively, these measurements can be used to significantly increase the accuracy of the DLW technique, introducing the possibility of extending this technique from population studies to the accurate assessment of the TEE of individual subjects. During Phase I, LGR will work with Professor Edward Melanson, an established researcher of metabolic studies, and Professor John Speakman, a key developer of the DLW method, to demonstrate a prototype instrument for measurements using vacuum-distilled, clinical samples. The correlation in background fluctuations between 2H/1H, 18O/16O, and 17O/16O from 40 humans will be quantified to demonstrate the applicability of using the 17O/16O signal to correct for background fluctuations in DLW experiments. Finally, two individuals will be measured using the DLW method to directly compare the conventional double isotope measurement to the newly-developed triple isotope measurement. At the conclusion of this research project, LGR will have demonstrated the use of the TIWA for DLW measurements and empirically determined the improvement in TEE accuracy and reduction in the DLW method cost due to the measurement of background fluctuation using 17O/16O. PUBLIC HEALTH RELEVANCE: The high prevalence of obesity in the US is a major public health concern, as overweight and obese individuals are at increased risk for many chronic diseases. Obesity stems from an imbalance between total caloric consumption and total energy expenditure, therefore accurate measurements of total energy expenditure (TEE) play a pivotal role in understanding and ultimately reversing this epidemic. This Small Business Innovative Research (SBIR) project will allow direct quantification of isotopic background fluctuation during doubly-labeled water measurements of TEE, potentially reducing the cost of isotope dose for TEE measurements from approximately $400 to $80 per adult subject and thereby greatly increasing the application of TEE measurements for obesity studies.

描述（由申请人提供）：美国肥胖症的高流行是一个主要的公共卫生问题，因为超重和肥胖的人对许多慢性疾病的风险增加。肥胖源于总热量消耗与总能量消耗（TEE）之间的不平衡，因此，准确的TEE测量在理解和最终逆转这种流行方面起着关键作用。在自由生活个体中测量T恤的黄金标准是双重标记的水（DLW）方法。 DLW方法的主要局限性包括高成本和精度仅为1 5％的单个测量结果。在这个小型企业创新研究（SBIR）项目中，Los Gatos Research（LGR）将开发，制造和测试一种基于激光的新型，基于激光的分析仪，以显着改善TEE的DLW测量，通过同时测量17o/16o以纠正18O和2H中的天然同位素波动，以使天然同位素波动纠正。 The Triple Isotope Water Analyzer (TIWA), which will be based on LGR's patented, laser-based Off-Axis ICOS technology, will be capable of real-time, simultaneous, high-throughput (50 samples/day) monitoring of 2H/1H, 18O/16O, and 17O/16O in H2O from human bodily fluids (e.g., blood, urine, and plasma), with a target accuracy of在2h/1h的10.60，18o/16o的10.20，在天然同位素丰度下为17o/16o的10.30。对于已标记为2H和18O的富集体水，目标精度将与同位素比率质谱相媲美，而2H/1H的质谱将比11.50，为18O/16o的10.50。 TIWA将允许在TEE测量过程中定量同位素背景波动，从而消除了在DLW实验过程中做出的显着“恒定背景”假设。同位素背景波动的测量将允许使用较小的同位素剂量，从而大大降低了TEE测量的成本。或者，这些测量值可用于显着提高DLW技术的准确性，从而引入了将该技术从人群研究扩展到对单个受试者TEE的准确评估的可能性。在第一阶段，LGR将与代谢研究的知名研究者爱德华·梅兰森（Edward Melanson）和DLW方法的主要开发商约翰·斯泰尔曼（John Speakman）教授一起演示了使用真空消耗，临床样本进行测量的原型工具。将量化2H/1H，18O/16O和17o/16o之间背景波动中的相关性，以证明使用17o/16o信号纠正DLW实验中的背景波动的适用性。最后，将使用DLW方法对两个人进行测量，以将常规的双同位素测量与新开发的三相同位素测量进行比较。在该研究项目的结论中，LGR将证明使用TIWA进行DLW测量，并通过经验确定TEE准确性的提高和DLW方法成本的降低，这是由于使用17o/16o的背景波动的测量结果。 公共卫生相关性：美国肥胖症的高流行是一个主要的公共卫生问题，因为超重和肥胖的人对许多慢性疾病的风险增加。肥胖源于总热量消耗和总能量消耗之间的不平衡，因此准确的总能量消耗（TEE）在理解和最终逆转这种流行方面起着关键作用。这项小型企业创新研究（SBIR）项目将允许在TEE的双标记水测量过程中直接量化同位素背景的波动，从而有可能将TEE测量的同位素剂量的成本从大约400美元降低到每个成人受试者的$ 40，从而大大增加了TEE测量的TEE测量obes obesity obesity研究。

项目成果

Measurement of δ18O, δ17O, and 17O-excess in water by off-axis integrated cavity output spectroscopy and isotope ratio mass spectrometry.

• DOI: 10.1021/ac402366t
• 发表时间: 2013-11-05
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Berman, Elena S. F.;Levin, Naomi E.;Landais, Amaelle;Li, Shuning;Owano, Thomas
• 通讯作者: Owano, Thomas