Developing a biomarker panel to assess choline nutritional status

开发生物标志物组来评估胆碱营养状况

基本信息

批准号：
9916222
负责人：
Steven H Zeisel
金额：
$ 15.24万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-24 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916222
关键词：
Back Biological Assay Biological Markers Bolus Infusion Chlorides Cholesterol Choline Choline Deficiency Clinical Collection Complement Consumption Data Data Analyses Data Collection Diet Dietary intake Fasting Fatty Liver Fatty acid glycerol esters Female Food Functional disorder Funding Health Human Image Institute of Medicine (U.S.)Intake Isotopes Laboratories Liver Magnetic Resonance Magnetic Resonance Spectroscopy Masks Mass Spectrum Analysis Measurement Measures Metabolic dysfunction Methodology Methods Modeling Muscle Nutrient Nutritional status Organ Outpatients Parents Participant Persons Phase Plasma Postmenopause Pregnancy Premenopause Procedures Public Health Practice Radioisotope Dilution Technique Randomized Risk Sampling Scientist Testing United States Urine Variant base biomarker panel dietary supplements elastography experimental study food avoidance genetic variant healthy volunteer in vivo in vivo magnetic resonance spectroscopy male metabolomics nutrition parent grant

项目摘要

Summary This request for a supplement to R01DK115380 is for funds for additional acquisition of magnetic resonance spectroscopy measures of choline content of liver in humans. The parent study seeks to develop a better biomarker panel that can be used by clinicians to assess a person's choline status. It has become apparent to us during the pilot phase of our studies that assessing Cho pool size using isotope dilution needs to be complemented by another accepted measure against which we can validate our metabolomic biomarker panel. We believe that using magnetic resonance spectroscopy to measure in vivo pools of soluble choline metabolites in liver needs to be added to our studies if we are to validate the metabolomic biomarker panel that we develop so as to convince clinicians that our metabolomic biomarker panel reliably predicts choline status. Choline is an important dietary supplement and essential nutrient, but there are no good validated biomarkers for assessing choline nutritional status that can be practically applied in clinical or public health practice. Choline is a required nutrient with Adequate Intake (AI) and a Tolerable Upper Limit (UL) levels set by the U.S. Institute of Medicine's Food and Nutrition Board and a Recommended Daily Intake (RDI). Given the narrow range for healthy intake of choline, given the establishment of a RDI of choline to maintain health, given the 3-fold variation in dietary intake in the US, given the effects of common genetic variants on requirements for choline and because plasma choline concentrations do not adequately reflect status, we propose that a panel of laboratory tests be developed and validated that assess choline status in humans. We will identify the biomarkers that best correlate with measurements of choline pool size using isotope dilution. Healthy volunteers (n=50 males, 50 premenopausal females and 50 postmenopausal females), as outpatients, will consume meals containing 100% of the RDI of choline (550 mg) for 2 weeks, 50% (275 mg) of the RDI of choline for 2 weeks, and 25% (137.5 mg) of the RDI of choline for 2 weeks. The order of dietary periods is randomly assigned and subjects and staff are masked. All subjects will receive all diets while on study, with a minimum of 2 weeks of “washout” between diet periods where participants go back to their normal diet. On Day 12 of each diet period, fasted subjects will consume a 250 mg bolus of choline in the form of Cho chloride-(trimethyl-d9). Plasma and urine samples will be collected for metabolomic assays and isotope dilution estimation of choline pool size and we will perform transient elastography of liver to assess liver fat. Magnetic resonance will also be used for independent assessment of choline status and liver fat. These studies will be used to determine the optimal set of biomarkers to use in calculating a choline status score.

概括此要求对R01DK115380进行补充，用于额外获得磁共振父母研究中肝的胆碱含量的光谱量。临床医生可以使用生物标志物小组评估一个人的胆碱状态。在我们的研究试点阶段，我们的我们需要使用同位素稀释来评估CHO池大小通过另一种公认的措施进行汇编，我们可以验证代谢组生物标志物面板。我们认为，使用磁共振光谱来测量近乎近乎近乎近的代谢物的体内库如果我们要验证我们开发的代谢组生物标志物面板，则需要将肝脏添加到我们的研究中为了说服临床医生，代谢组生物标志物面板预测胆碱状态重要的饮食补充剂和必需的养分胆碱营养状况实际上可以应用于临床或公共卫生实践。摄入量（AI）和美国医学研究所设定的可容忍的上限（UL）水平（UL）的营养素食品和营养委员会和建议的每日摄入量（RDI）。考虑到饮食摄入量的3倍变化，胆碱是胆碱的建立以维持健康在美国，鉴于常见遗传变异对胆碱需求的影响和血浆胆碱的影响浓度不能充分重新置换状态，我们建议开发一组实验室测试，并验证了评估人类的胆碱状态。使用同位素稀释的胆碱池大小。女性和50个绝经后女性）作为门诊病人，将食用餐点100％胆碱（550 mg）持续2周，胆碱RDI的50％（275 mg）持续2周，RDI的25％（137.5 mg）胆碱的饮食时期是随机分配的。受试者在学习时将接受所有饮食参与者在每个饮食期的第12天都可以接受250毫克胆碱的推注，以Cho氯化物的形式（三甲基-D9）。代谢组分测定和胆碱池大小的同位素稀释，我们将执行短暂的肝脏评估肝脂肪的弹性也将用于独立评估胆碱状态和肝脂肪将用于确定最佳的生物标志物计算胆碱状态得分。