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Investigation of pathogenesis of hyperuricemia based on untargeted and targeted metabolomics.

ABSTRACT: Hyperuricemia (HUA) seriously harms human health but the exact etiology and pathogenesis of HUA are not fully understood. Therefore, it is still of great significance to find effective biomarkers and explore the pathogenesis of HUA. Metabolomics reflects the influence of internal and external factors on system metabolism, explains the changes in metabolite levels during the development of diseases, and reveals the molecular mechanism of pathogenesis. Metabolomics is divided into untargeted metabolomics and targeted metabolomics according to different research modes. Each other's advantages can be fully utilized by combining the two so that the results of metabolomics research can be consummated. 20 HUA patients and 20 healthy individuals participated in the experiment, and untargeted metabolomics was employed to find 50 differential metabolites in HUA serum samples. Twelve candidate biomarkers were screened based on literature research and ROC Curve analysis for subsequent verification. Based on the UPLC-TQ-MS analysis platform, the targeted metabolomics detection methods were established and the content of 12 candidate biomarkers was precisely quantified. Compare with the results of untargeted metabolomics, the targeted metabolomics results were considered more reliable.

SUBMITTER: Qin N

PROVIDER: S-EPMC9386008 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Investigation of pathogenesis of hyperuricemia based on untargeted and targeted metabolomics.

Qin Nankun N Qin Ming M Shi Wenjun W Kong Lingbo L Wang Liting L Xu Guang G Guo Yuying Y Zhang Jiayu J Ma Qun Q

Scientific reports 20220817 1

Hyperuricemia (HUA) seriously harms human health but the exact etiology and pathogenesis of HUA are not fully understood. Therefore, it is still of great significance to find effective biomarkers and explore the pathogenesis of HUA. Metabolomics reflects the influence of internal and external factors on system metabolism, explains the changes in metabolite levels during the development of diseases, and reveals the molecular mechanism of pathogenesis. Metabolomics is divided into untargeted metab ...[more]

PMID: 35978088

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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.

Project description:As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has become the major factor responsible for the noninfectious cause of mortality in laying hens, which lead to huge economic losses to poultry industry. However, the pathogenesis of FLHS remains unclear. The aim of present study was to identify novel liver metabolites associated with FLHS. Twenty healthy Chinese commercial Jing Fen laying hens aged 90 d were used in present study. After acclimatization for 2 wk, the hens were divided into 2 treatments (n = 10): control group (normal diet) and FLHS group (high-energy low-protein diet). The experiment lasted for 48 d, and the laying hens were killed for blood and liver sampling at the end of the experiment. Blood biochemical indicators and liver pathological changes were examined. Meanwhile, the changes in liver metabolic profile were investigated with the application of metabolomics approach. Significant increased levels of alanine aminotransferase, aspartate aminotransferase, low density lipoprotein, total cholesterol and triglycerides, decreased high density lipoprotein (P < 0.01), and hepatic steatosis were observed in hens of FLHS group, which suggested FLHS was successfully established in this study. Distinct changes in metabolite patterns in liver between control and FLHS group were observed by partial least-squares discriminant analysis. In total, 42 liver metabolites including tyrosine, glutathione, carnitine, linoleic acid, uric acid, arachidonic acid (ARA), lactate and lysophosphatidylcholine (14: 0) were identified and considered to be related with pathogenesis of FLHS. Pathway analysis revealed that these metabolites were mainly involved in amino acid metabolism, fatty acid metabolism, ARA metabolism, glucose metabolism and glycerophospholipid metabolism. Furthermore, targeted metabolomics found that ARA metabolites such as prostaglandins and hydroxyeicosatetraenoic acids were significantly increased in FLHS group (P < 0.05). In conclusion, our data showed that liver metabolites and ARA metabolism were linked to the pathophysiology of FLHS, which provided a basis for understanding the pathogenesis of FLHS in laying hens.

Dataset Information

Investigation of pathogenesis of hyperuricemia based on untargeted and targeted metabolomics.

Publications

Investigation of pathogenesis of hyperuricemia based on untargeted and targeted metabolomics.

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