Abstract
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.
Highlights
Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders and is an important risk factor for gout, cardiovascular disease, metabolic syndrome, and so on [1,2,3,4,5,6]
With the improvement of living standards, more high-purine, high-protein, and highcalorie foods have entered people’s diet structure [7]; the prevalence of HUA is on the rise globally with the trend of younger age [8,9,10,11,12,13,14]. e etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. erefore, it is of great significance to explore metabolic disorders in vivo and the pathogenesis of HUA from the perspective of metabolomics
Extensive studies have been extensively conducted on HUA metabolomics, but these studies were mainly focused on animal experiments and there is little research describing HUA metabolic disorders in humans [21,22,23,24,25]
Summary
Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders and is an important risk factor for gout, cardiovascular disease, metabolic syndrome, and so on [1,2,3,4,5,6]. Erefore, it is of great significance to explore metabolic disorders in vivo and the pathogenesis of HUA from the perspective of metabolomics. Metabolomics analysis explores the dynamic changes of endogenous small molecule substances (saccharides, organic acids, lipids, amino acids, etc.) at a certain stage of the disease [15]. E integrity of the extraction of endogenous small molecular substances from biological samples is tremendously important for the analysis results. Organic solvent protein precipitation (PPT) is simple, economical, and easy to perform that has usually been regarded as the most commonly used extract method for serum samples prior to metabolomics analysis [29, 30]. We have analyzed the relationship between several precipitation solvents of PPT and the analysis results and subsequently recommend appropriate protocols of serum preparation for HUA metabolomics analysis
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