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.

胆碱是一种重要的和必需的营养素，但没有良好的验证生物标志物用于评估胆碱营养状况，可实际应用于临床或公共卫生实践。胆碱是一种必需的营养素，由美国医学研究所食品和营养委员会和推荐每日摄入量（RDI）设定的充足摄入量（AI）和可耐受上限（UL）水平。鉴于胆碱的健康摄入量范围狭窄，鉴于建立了维持健康的胆碱RDI，鉴于美国饮食摄入量的3倍变化，鉴于常见遗传变异对胆碱需求的影响，以及由于血浆胆碱浓度不能充分反映状态，我们建议开发并验证一组实验室测试，以评估人类胆碱状态。从更大的一组措施，我们将确定的生物标志物的措施，最好的相关性使用同位素稀释胆碱池大小的测量。健康志愿者（n=60名男性，60名绝经前女性和60名绝经后女性），作为门诊患者，将食用含有100%推荐摄入量胆碱的膳食（550毫克胆碱/天）2周，然后他们将被转换为含有50%的胆碱推荐摄入量的饮食2周，然后改为饮食中含有25%的推荐摄入量的胆碱2周，然后改为饮食中含有10%的推荐摄入量的胆碱（55 mg胆碱）2周。最后，所有受试者将接受100%胆碱饮食2周的胆碱补充。在每个饮食期的最后3天，受试者将摄入氘代胆碱。将采集血浆和尿液样本进行代谢组学测定（在先前研究中确定的生物标志物小分子可能预测胆碱状态），胆碱池大小的同位素稀释估计，我们将进行肝脏瞬时弹性成像以评估肝脏脂肪。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组，该评分与使用同位素稀释评估的胆碱池大小密切相关。最后，胆碱和叶酸代谢基因中的SNPs与低胆碱饮食引起器官功能障碍的风险增加有关。我们将通过确定具有这些SNP的人是否具有比没有这些SNP的人更低的胆碱池大小/更差的胆碱状态评分来测试我们的胆碱状态评分。