Identification of the urine and serum metabolomics signature of gout

Huang, Yefei; Xiao, Min; Ou, Jiamin; Lv, Qing; Wei, Qiujing; Chen, Zena; Wu, Jialing; Tu, Liudan; Jiang, Yutong; Zhang, Xi; Qi, Jun; Qiu, Minli; Cao, Shuangyan; J, Gu

doi:10.1093/rheumatology/keaa018

Cited by 27 publications

(39 citation statements)

References 25 publications

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“…Rats with hyperuricemia induced by fructose showed decreased levels of isoleucine and valine in plasma [ 36 ]. However, contrary to our results, elevated levels of leucine and valine in serum were observed in gout patients [ 37 ]. The discrepant results may be due to differences in metabolism between humans and animals.…”

Section: Discussioncontrasting

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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Section: Discussioncontrasting

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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“…The main function of CrAT in peroxisomes is to aid in the export of products of peroxisomal b-oxidation (Westin et al, 2008). In the murine cardiomyocyte cytosol, the (Forni et al, 2010); glutaric aciduria type 2 (Forni et al, 2010); ethylmalonic encephalopathy (Forni et al, 2010); gestational diabetes (Roy et al, 2018) Decreased Traumatic brain injury (Jeter et al, 2013) Urine Increased Glutaric aciduria type 2 (Sugiyama et al, 1990); multiple acyl-CoA dehydrogenase deficiency (Kidouchi et al, 1988); acute coronary syndrome (Wang et al, 2018) Isovalerylcarnitine (C5:0 I) Blood Increased Isovaleric acidemia (Shigematsu et al, 2007;Forni et al, 2010;Couce et al, 2017;Lin et al, 2020); glutaric aciduria type 2 (Forni et al, 2010); 3hydroxy-3-methylglutaryl-CoA lyase deficiency (Ma et al, 2011;V aclav ık et al, 2020); cardiovascular diseases (Kukharenko et al, 2020); acute kidney injury (Wan et al, 2019) Decreased Daytime sleepiness (Pak et al, 2018); inflammatory bowel disease (Danese et al, 2011); ulcerative colitis (Bene et al, 2006); traumatic brain injury (Jeter et al, 2013) Urine Increased Glutaric aciduria type 2 (Shimizu et al, 1991); multiple acyl-CoA dehydrogenation deficiency (Kidouchi et al, 1988) 2-Methylbutyrylcarnitine (C5:0 M) Blood Increased Short/branched-chain acyl-CoA dehydrogenase deficiency/2-methylbutyryl-CoA dehydrogenase deficiency (Madsen et al, 2006;Forni et al, 2010); glutaric aciduria type 2 (Forni et al, 2010); gout (Huang et al, 2020); nonalcoholic steatohepatitis (Kalhan et al, 2011) Decreased Pediatric obesity (Farook et al, 2015); traumatic brain injury (Jeter et…”

Section: A Enzymology Of Acylcarnitine Biosynthesismentioning

confidence: 99%

Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials

et al. 2022

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“…2B ). Uric acid is known for its inductive function in pathogenesis of GA ( Huang et al, 2020 ). Remarkably, levels of IL-22 and VD-R closely correlated with the uric acid levels in the serum of both HC and GA patients.…”

Section: Resultsmentioning

confidence: 99%

Functions of 1,25-dihydroxy vitamin D3, vitamin D3 receptor and interleukin-22 involved in pathogenesis of gout arthritis through altering metabolic pattern and inflammatory responses

Chen¹,

et al. 2021

PeerJ

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Background Gouty arthritis (GA) is a common type of inflammatory arthritis. Recent studies demonstrated that 1,25-dihydroxy vitamin D3 (1,25(OH) 2 VD3) and vitamin D3 receptor (VD-R) play a protective role in acute inflammation, but interleukin-22(IL-22) promotes inflammation, especially for arthritis. However, our understanding of the responses of 1,25(OH) 2VD3 and IL-22 to gout was still unclear. Presently, in-depth metabolomics, bioinformatics and clinical characteristics analyses were performed to elucidate the pathogenesis and valuable clinical indicators of gouty arthritis. Methods Peripheral venous blood was taken for investigation. The levels of IL-22 and 1,25(OH)2VD3 were determined in patient’s plasma via ELISA, and the mRNA levels of IL-22 and VD-R were measured via qRT-PCR. The interaction network of VD-R and IL22 were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the biological function of the related proteins were analyzed by Clusterprofiler Metabolomics were performed to decipher the metabolic variations of GA. Results The levels of VD-R and 1,25(OH) 2 VD3 were identified to be low. What,s more, GA patients were reported to have high expression of IL-22. And IL-22 levels positively correlated with C-reactiveprotein (CRP) serum levels in the bivariate correlation analysis, whereas the level of 1,25(OH) 2VD3 negatively correlated with that of CRP. GO and KEGG analyses revealed that IL-22 and 1,25(OH) 2 VD3 were involved in stress immunity and inflammatory responses. These pathways are known to play a role in GA pathogenesis. Meanwhile, the metabolic profiles of GA serum showed that the increase in various amino acids and uric acid are involved in GA pathogenesis. Importantly, VD-R and IL22 closely correlated with the level of key metabolites uric acid, whose increase promoted the occurrence of GA. Conclusion GA patients have low levels of VD-R and 1,25(OH) 2 VD3, and high levels of IL-22 together with various amino acids and uric acid. The levels of IL-22 and 1,25(OH) 2VD3 were positively and negatively correlated with C-reactive protein (CRP) serum levels, respectively. Both IL-22 and 1,25(OH) 2 VD3 functioned in GA-related immune and inflammatory responses, and closely correlated with the level of GA-related uric acid. Overall, IL-22, VD-R and 1,25(OH) 2 VD3 play functionally important roles in inflammatory responses and are relevant to gout pathogenesis.

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Identification of the urine and serum metabolomics signature of gout

Cited by 27 publications

References 25 publications

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

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

Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials

Functions of 1,25-dihydroxy vitamin D3, vitamin D3 receptor and interleukin-22 involved in pathogenesis of gout arthritis through altering metabolic pattern and inflammatory responses

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