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Serum biomarkers of the calcium-deficient rats identified by metabolomics based on UPLC/Q-TOF MS/MS.

ABSTRACT: Background: We previously identified the urinary biomarkers to diagnose calcium deficiency and nutritional rickets by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS). To find biomarkers of calcium deficiency and further confirm these biomarkers in serum, we performed serum metabolomics analysis of calcium-deficient rats.

Methods: A calcium-deficient rat model was established with a low-calcium diet for 12 weeks. Serum metabolomics based UPLC/Q-TOF MS/MS and multivariate statistical analysis was performed to identify the alterations in metabolites associated with calcium deficiency in rats.

Results: Bone mineral density, serum parathyroid hormone and alkaline phosphatase were significantly decreased in the low-calcium diet group (LCG) compared to the normal calcium diet group (NCG). Serum metabolic-profiling analysis could definitively distinguish between the LCG and NCG and identified 24 calcium-deficient biomarkers. Three metabolites (indoxyl sulfate, phosphate, and taurine) of the 24 biomarkers were found in our previous urinary metabolomics study of rats with a calcium deficiency and nutritional rickets. The areas under the curve (AUCs) of these three biomarkers were greater than 0.8, and the combination of any two biomarkers was higher than 0.95.

Conclusion: Dietary calcium deficiency induced the alterations of metabolites in the serum of rats, and the three identified biomarkers had relatively high diagnostic values for calcium deficiency in rats.

SUBMITTER: Meng F

PROVIDER: S-EPMC7708254 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Serum biomarkers of the calcium-deficient rats identified by metabolomics based on UPLC/Q-TOF MS/MS.

Meng Fanyu F Fan Lina L Sun Lin L Yu Qingli Q Wang Maoqing M Sun Changhao C

Nutrition & metabolism 20201123 1

<h4>Background</h4>We previously identified the urinary biomarkers to diagnose calcium deficiency and nutritional rickets by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS). To find biomarkers of calcium deficiency and further confirm these biomarkers in serum, we performed serum metabolomics analysis of calcium-deficient rats.<h4>Methods</h4>A calcium-deficient rat model was established with a low-calcium diet for 12 weeks. Serum met ...[more]

PMID: 33292300

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Project description:Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and α-linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and a-linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.

Dataset Information

Serum biomarkers of the calcium-deficient rats identified by metabolomics based on UPLC/Q-TOF MS/MS.

Publications

Serum biomarkers of the calcium-deficient rats identified by metabolomics based on UPLC/Q-TOF MS/MS.

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