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

• 批准号: 10066347
• 负责人: Steven H Zeisel
• 金额: $ 62.77万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-08 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066347
• 关键词: Age; Biological Assay; Biological Markers; Child; Cholesterol; Choline; Choline Deficiency; Clinical; Consumption; Data; Diet; Dietary intake; Eating; Fatty Liver; Fatty acid glycerol esters; Feces; Female; Food; Functional disorder; Genes; Genetic Polymorphism; Health; Hepatic Mass; Human; Image; Institute of Medicine (U.S.); Intake; Isotopes; Label; Laboratories; Liver; Measurement; Measures; Metabolic dysfunction; Methodology; Modeling; Muscle; Nutrient; Nutritional status; Organ; Outpatients; Persons; Plasma; Postmenopause; Pregnancy; Premenopause; Proxy; Public Health Practice; Radioisotope Dilution Technique; Risk; Sampling; Scientist; Spectrum Analysis; Study Subject; Testing; United States; Urine; Variant; base; biomarker panel; elastography; experimental study; folic acid metabolism; food avoidance; genetic variant; healthy volunteer; improved; male; metabolomics; nutrition; small molecule

Choline is an important 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. From a larger set of measures, we will identify the biomarker measures that best correlate with measurements of choline pool size using isotope dilution. Healthy volunteers (n=60 males, 60 premenopausal females and 60 postmenopausal females), as outpatients, will consume meals containing 100% of the recommended intake of choline (550 mg choline/day) for 2 weeks, they will then be switched to a diet containing 50% of the recommended intake of choline for 2 weeks, then switched to a diet containing 25% of the recommended intake of choline for 2 weeks, and then switched to a diet containing 10% of the recommended intake of choline (55 mg choline) for 2 weeks. Finally, all subjects will be placed on the 100% choline diet for 2 weeks of choline repletion. On the last 3 days of each diet period, subjects will consume deuterated choline. Plasma and urine samples will be collected for metabolomic assays (biomarker small molecules identified in a previous study as likely to predict choline status), isotopic dilution estimation of choline pool size and we will perform transient elastography of liver to assess liver fat. These studies will be used to determine the optimal set of biomarkers to use in calculating a choline status score that correlates well with choline pool size assessed using isotope dilution. Finally, SNPs in genes of choline and folate metabolism have been associated with increased risk for developing organ dysfunction on a low choline diet. We will test our choline status score by determining whether people with these SNPs have a lower choline pool size/worse choline status score for any given choline dietary intake than do people without these SNPs.

胆碱是重要且重要的营养素，但是没有良好的验证生物标志物可以评估胆碱营养状况，这实际上可以用于临床或公共卫生实践中。胆碱是所需的营养素，具有足够的摄入量（AI）和美国医学研究所食品和营养委员会设定的可忍受的上限（UL）水平，并推荐的每日摄入量（RDI）。鉴于在美国饮食摄入的3倍变化，鉴于胆碱的健康摄入范围狭窄，鉴于普通遗传变异对胆碱的需求和血浆胆碱的影响，因此维持健康。浓度不能充分反映状态，我们建议开发和验证一组实验室测试，以评估人类的胆碱状态。从一组较大的措施中，我们将确定使用同位素稀释的胆碱池大小相关的生物标志物测量。健康的志愿者（n = 60名男性，60个绝经前女性和60个绝经后女性），因为门诊病人将食用含有100％推荐胆碱摄入量的100％（550毫克胆碱/天）的餐食，然后将其切换到一个，然后将其切换到一个。饮食中含有50％的建议胆碱摄入量2周，然后切换为含有25％推荐胆碱摄入量的25％的饮食，然后切换为含有建议胆碱摄入量的10％的饮食（55 mg）胆碱）持续2周。最后，所有受试者将在100％的胆碱饮食上进行2周的胆碱补充。在每个饮食期的最后3天，受试者将食用氘代胆碱。将收集血浆和尿液样品以进行代谢组学测定（先前研究中鉴定出的生物标志物小分子可能预测胆碱状态），同位素稀释量的胆碱池尺寸估计，我们将执行肝脏的短暂弹性弹性，以评估肝脏脂肪。这些研究将用于确定用于计算胆碱状态评分的最佳生物标志物集合，该评分与使用同位素稀释度评估的胆碱池尺寸非常相关。最后，胆碱和叶酸代谢基因的SNP与低胆碱饮食中器官功能障碍的风险增加有关。我们将通过确定与没有这些SNP的人相比，任何给定的胆碱饮食摄入量的胆碱池大小/胆碱状态得分较低/胆碱状态得分较差，我们将测试我们的胆碱状态得分。