High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS
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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.Keywords:
Metabolic pathway
Fatty Acid Metabolism
Glucuronates
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Glucuronates
Metabolic pathway
Metabolome
Hippuric acid
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Alcoholic liver disease (ALD) is a significant cause of death and morbidity. However little is known regarding the widespread pathway changes of ALD disorder. This study utilized metabolomic profiling to examine the pathogenic mechanisms of ALD based on a rat model. A total of 21 metabolites with significant changes were identified, involving several key metabolic pathways such as pentose and glucuronate interconversions, starch and sucrose metabolism, cysteine and methionine metabolism. Furthermore, the differential proteins corresponding to alterations in metabolism across the metabolic network were identified using iTRAQ-based quantitative proteomics analysis. The proteins appear to be involved in protein binding, metabolism, immune response, and signal conduction. Interestingly, integrated omics profiling firstly reveals that p53 and Fc epsilon RI signaling pathways were closely related to ALD. Our study indicates that most of these proteins were found to play a pivotal role in the regulation of multiple metabolism pathways. Collectively, the current study provides insights into the molecular mechanisms of ALD from widespread pathway changes.
Glucuronates
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Cysteine Metabolism
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Pathway Analysis
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Nutrient flow to the embryo and placenta is crucial for proper development and growth during pregnancy. In this study, a metabonomic analysis was undertaken to better understand global changes in pregnant dairy cows on D 17 and D 45 after timed artificial insemination (AI). Metabolic changes in the blood plasma of pregnant dairy cows were investigated using HPLC-MS and a multivariate statistical analysis. Changes in metabolic networks were established using the MetPA method. Alterations in six metabolic pathways were found on D 17 and D 45, including variations in the level of alpha-linolenic acid metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, glycerolipid metabolism, folate biosynthesis, and tyrosine metabolism. In addition to these pathways, 9 metabolic pathways were markedly altered on D 45. These pathways included changes in the one-carbon pool caused by folate; phenylalanine, tyrosine and tryptophan biosynthesis; thiamine metabolism; pantothenate and CoA biosynthesis; purine metabolism; inositol phosphate metabolism; amino sugar and nucleotide sugar metabolism; pentose phosphate; and the TCA pathway. The combination of metabonomics and network methods used in this study generated rich biochemical insight into possible biological modules related to early pregnancy in dairy cows.
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Abstract Coronary heart disease (CHD) is the result of a complex metabolic disorder caused by various environmental and genetic factors, and often has anxiety as a comorbidity. Rupture of atherosclerotic plaque in CHD patients can lead to acute coronary syndrome (ACS). Anxiety is a known independent risk factor for the adverse cardiovascular events and mortality in ACS, but it remains unclear how stress-induced anxiety behavior impacts their blood plasma metabolome and contributes to worsening of CHD. The present study aimed to determine the effect of anxiety on the plasma metabolome in ACS patients. After receiving ethical approval 26 ACS patients comorbid anxiety were recruited and matched 26 ACS patients. Blood plasma samples were collected from the patients and stored at − 80 °C until metabolome profiling. Metabolome analysis was performed by liquid chromatography mass spectrometry (LC–MS), and the data were subjected to multivariate analysis. Disturbance of 39 plasma metabolites was noted in the ACS with comorbid anxiety group compared to the ACS group. These disturbed metabolites were mainly involved in tryptophan metabolism, pyrimidine metabolism, glycerophospholipid metabolism, pentose phosphate pathway, and pentose and glucuronate interconversions. The most significantly affected pathway was tryptophan metabolism including the down-regulation of tryptophan and serotonin. Glycerophospholipids metabolism, pentose and glucuronate interconversions, and pentose phosphate pathway were also greatly affected. These results suggest that anxiety can disturb three translation of material in ACS patients. Besides the above metabolism pathways pyrimidine metabolism was significantly disturbed. Based on the present findings the plasma metabolites monitoring can be recommended and may be conducive to early biomarkers detection for personalized treatment anxiety in CHD patients in future.
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Fatty Acid Metabolism
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According to traditional Chinese medicine theory, tongue coatings reflect changes in the body. The goal of this study was to identify a metabolite or a set of metabolites capable of classifying characteristics of traditional Chinese medicine syndromes in erosive gastritis. In this study, we collected tongue coatings of patients with erosive gastritis with damp-heat syndrome (DHS), liver depression and qi stagnation syndrome (LDQSS), and healthy volunteers. Then, we analyzed the differences in metabolic characteristics between the two groups based on metabolomics. We identified 14 potential biomarkers related to the DHS group, and six metabolic pathways were enriched. The differential pathways included pyrimidine metabolism, pantothenate and CoA biosynthesis, citrate cycle (TCA cycle), pyruvate metabolism, glycolysis/gluconeogenesis, and purine metabolism. Similarly, in the LDQSS group, we identified 25 potential biomarkers and 18 metabolic pathways were enriched. The top five pathways were the TCA cycle, sphingolipid metabolism, fatty acid biosynthesis, pantothenate and CoA biosynthesis, and the pentose phosphate pathway. In conclusion, the DHS group and the LDQSS group have different characteristics.
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Glucuronates
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As a classic prescription, Huangqin Tang (HQT) has been widely applied to treat ulcerative colitis (UC), although its pharmacological mechanisms are not clear. In this study, urine metabolomics was first analysed to explore the therapeutic mechanisms of HQT in UC rats induced by TNBS. We identified 28 potential biomarkers affected by HQT that might cause changes in urine metabolism in UC rats, mapped the network of metabolic pathways, and revealed how HQT affects metabolism of UC rats. The results showed that UC affects amino acid metabolism and biosynthesis of unsaturated fatty acids and impairs the tricarboxylic acid cycle (TCA cycle). UC induced inflammatory and gastrointestinal reactions by inhibiting the transport of fatty acids and disrupting amino acid metabolism. HQT plays key roles via regulating the level of biomarkers in the metabolism of amino acids, lipids, and so on, normalizing metabolic disorders. In addition, histopathology and other bioinformatics analysis further confirm that HQT altered UC rat physiology and pathology, ultimately affecting metabolic function of UC rats.
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Fatty Acid Metabolism
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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.
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Fatty Acid Metabolism
Glucuronates
Metabolome
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To illustrate the metabolic regulatory mechanisms of Jiangzhi decoction (JZD) against non-alcoholic fatty liver disease (NAFLD).High-fat diet (HFD)-induced NAFLD rats were treated with JZD. The pathological morphology, lipid indexes and liver function were detected. Metabolic profiles were examined by liquid chromatography-mass spectrometry (LC-MS). Multivariate and univariate statistical analysis were used to search the differential metabolites. Pathway enrichment analysis was carried out using Kyoto Encyclopedia of Genes and Genomes database. Compound-gene networks were built by Cytoscape software.JZD significantly alleviated the pathological conditions and improved lipid index levels. Multivariate analysis showed a good separation among different groups. Three hundred and twenty-seven metabolites in HFD versus control and 301 metabolites in JZD versus HFD were identified to be significantly different. Pathway enrichment analysis showed that lipid metabolism pathways were prominent altered pathways. Importantly, the relationships were more distant between JZD and HFD groups in all five lipid metabolism pathways, including arachidonic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism and sphingolipid metabolism, while those were obviously closer between JZD and control groups. Simultaneously, JZD treatment restored the levels of disturbed differential metabolites in HFD group.JZD had an effect on alleviating NAFLD via regulating relevant lipid metabolism.
Glycerophospholipids
Metabolic pathway
Fatty Acid Metabolism
KEGG
Decoction
Sphingolipid
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Plateau adaptation in animals involves genetic mechanisms as well as coevolutionary mechanisms of the microbiota and metabolome of the animal. Therefore, the characteristics of the rumen microbiome and metabolome, transcriptome, and serum metabolome of Tibetan sheep at different altitudes (4500 m, 3500 m, and 2500 m) were analyzed. The results showed that the rumen differential metabolites at 3500 m and 4500 m were mainly enriched in amino acid metabolism, lipid metabolism, and carbohydrate metabolism, and there was a significant correlation with microbiota. The differentially expressed genes and metabolites at middle and high altitudes were coenriched in asthma, arachidonic acid metabolism, and butanoate and propanoate metabolism. In addition, the serum differential metabolites at 3500 m and 4500 m were mainly enriched in amino acid metabolism, lipid metabolism, and metabolism of xenobiotics by cytochrome P450, and they were also related to microbiota. Further analysis revealed that rumen metabolites accounted for 7.65% of serum metabolites. These common metabolites were mainly enriched in metabolic pathways and were significantly correlated with host genes (p < 0.05). This study found that microbiota, metabolites, and epithelial genes were coenriched in pathways related to lipid metabolism, energy metabolism, and immune metabolism, which may be involved in the regulation of Tibetan sheep adaptation to plateau environmental changes.
Metabolome
Fatty Acid Metabolism
Metabolic pathway
Carbohydrate Metabolism
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