Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis.
Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis.
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通过综合尿液代谢组学分析进行缺钙评估和生物标志物鉴定
DOI：
10.1186/1741-7015-11-86
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发表时间：
2013-03-28
期刊：
影响因子：
9.3
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Wang M;Yang X;Wang F;Li R;Ning H;Na L;Huang Y;Song Y;Liu L;Pan H;Zhang Q;Fan L;Li Y;Sun C
背景钙缺乏是一个全球性的公共卫生问题。虽然缺钙的初始阶段可导致代谢改变或潜在的病理变化，但缺钙很难准确诊断。此外，钙缺乏的分子机制的细节仍然有些难以捉摸。为了准确地评估和提供适当的营养干预，我们进行了一个全球性的分析，响应钙deficiency.MethodsThe代谢改变与钙缺乏相关的第一次在大鼠模型中进行了调查，使用尿代谢组学的基础上超高效液相色谱法与四极杆飞行时间串联质谱和多元统计分析。膳食钙摄入量和从大鼠模型中确定的生物标志物之间的相关性进行了进一步分析，以确认这些生物标志物在human.ResultsUrinary代谢分析的潜在应用可以初步区分钙缺乏和非缺乏大鼠2周低钙饮食后。我们建立了一个综合的代谢组学策略，用于识别可靠的生物标志物的钙缺乏症使用的时间过程分析的歧视代谢物在低钙饮食实验，重复低钙饮食实验和进行补钙实验。总共鉴定了27种生物标志物，包括甘氨酸、氧代谷氨酸、焦磷酸、癸二酸、假尿苷、硫酸吲哚酚、牛磺酸和苯乙酰甘氨酸。综合尿代谢组学分析将尿中的生物标志物与有规律的变化趋势（A、B、C型）相结合，能准确评估不同阶段的钙缺乏大鼠，详细阐明钙缺乏的动态病理生理变化和分子机制。钙摄入量和两个生物标志物，假尿苷（Pearson相关系数，r= 0.53，P = 0.0001）和柠檬酸盐（Pearson相关系数，r=-0.43，P = 0.001）之间的显着相关性，进一步证实了70 women.ConclusionsTo我们所知，这是第一个可靠的钙缺乏的生物标志物，这是确定使用一个综合的策略报告。这些生物标志物为钙缺乏的病理生理变化和分子机制提供了新的见解。钙摄入量与两种生物标志物之间的相关性为进一步评估和阐明人类钙缺乏的代谢反应提供了理论基础或潜力。
BackgroundCalcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency.MethodsThe metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans.ResultsUrinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson correlation,r= 0.53,P= 0.0001) and citrate (Pearson correlation,r= -0.43,P= 0.001), were further confirmed in 70 women.ConclusionsTo our knowledge, this is the first report of reliable biomarkers of calcium deficiency, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of calcium deficiency. The correlations between calcium intake and two of the biomarkers provide a rationale or potential for further assessment and elucidation of the metabolic responses of calcium deficiency in humans.
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影响因子：
4.4
作者：
Manna SK;Patterson AD;Yang Q;Krausz KW;Li H;Idle JR;Fornace AJ Jr;Gonzalez FJ
通讯作者：
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