Lipidomics coupled with pathway analysis characterizes serum metabolic changes in response to potassium oxonate induced hyperuricemic rats

Yang, Fei; Li, Mingyu; Qin, Nankun; Li, Shuangshuang; Yu, Mengqi; Wang, Chengxiang; Ma, Qun

doi:10.1186/s12944-019-1054-z

Cited by 28 publications

(17 citation statements)

References 20 publications

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“…The metabolites involved in glycerophospholipid metabolism and sphingolipid metabolism account for a large proportion of all metabolites, prompting attention to the correlation between abnormal lipid metabolism and HUA. In the previous study of HUA rat model by potassium oxonate or fructose in our laboratory [ 25 , 40 ], glycerophospholipid metabolism was implicated. A large number of glycerophospholipids and their metabolites in serum samples of HUA patients were disturbed; phospholipid metabolism disorder occurred; PC, LysoPC, PE, LysoPE, PI, LysoPI, PS, PG, PGP, and LysoPA were mainly involved.…”

Section: Discussionmentioning

confidence: 99%

“…e study of metabolic disorders is meant for assisting disease, clinical diagnosis, screening of therapeutic drugs and targets [18][19][20]. Over recent years, 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].…”

Section: Introductionmentioning

confidence: 99%

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High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS

Qin

Yue

Shi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS

Qin

Yue

Shi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The enhancement of PLA2 and LPCAT3 activity results in accelerated glycerophospholipid metabolism, so the levels of PC and LPC were both up-regulated in HUA rats. In our previous studies, PEs are key biomarkers of potassium oxonate induced HUA rats [ 57 ]. Interestingly, we also found that PE(18:3/22:4) and PE(24:1/24:1) are the key biomarkers in the treatment of HUA with Plantaginis Semen this time.…”

Section: Discussionmentioning

confidence: 99%

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

Yang

Shi

Wang

et al. 2021

BMC Complement Med Ther

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Background Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. Methods A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875 or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Results Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was most affected. These perturbations were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. Conclusions Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.

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“…If sufficient carbohydrates are not available, the body begins to metabolize fats into ketone bodies ( β -hydroxybutyrate and acetoacetate) to provide the necessary fuel. Lipidomics studies revealed that saturated fatty acid LPCs were upregulated and unsaturated fatty acid LPCs were downregulated in potassium oxonate-induced hyperuricemic rats [ 31 ], while increased levels of all PCs and unsaturated fatty acid LPCs together with decreased levels of saturated fatty acid LPCs were detected in rats with hyperuricemia induced by fructose [ 32 ]. These contrary conclusions might be due to different model-making methods.…”

Section: Discussionmentioning

confidence: 99%

NMR-Based Metabonomic Study Reveals Intervention Effects of Polydatin on Potassium Oxonate-Induced Hyperuricemia in Rats

Han

Gong

Zhong

et al. 2020

Oxidative Medicine and Cellular Longevity

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Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.

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Lipidomics coupled with pathway analysis characterizes serum metabolic changes in response to potassium oxonate induced hyperuricemic rats

Cited by 28 publications

References 20 publications

High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS

High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

NMR-Based Metabonomic Study Reveals Intervention Effects of Polydatin on Potassium Oxonate-Induced Hyperuricemia in Rats

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