Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population

Furuhashi, Masato; Matsumoto, Megumi; Tanaka, Marenao; Moniwa, Norihito; Murase, Takayo; Nakamura, Takashi; Ohnishi, Hirofumi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

doi:10.1253/circj.cj-18-0082

Cited by 75 publications

(99 citation statements)

References 42 publications

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“…It has been suggested that high plasma XOR activity is a metabolic parameter that is superior to uric acid level, and that adequately inhibiting plasma XOR activity unless lowering uric acid would be a new therapeutic strategy for treatment of metabolic and cardiovascular diseases. It has also been reported that unexpected high plasma XOR activities possibly associated with liver dysfunction and insulin resistance are found in some women with a relatively low level of uric acid in a general population.…”

Section: Discussionmentioning

confidence: 99%

“…In a population‐based cohort, the Tanno‐Sobetsu Study, a total of 627 Japanese participants (male/female: 292/335) were recruited from residents of Sobetsu Town in 2016. This population was the same as that in our previous study for investigating plasma XOR activity. Participants treated with any medications were excluded for the elimination of drug effects on plasma XOR activity and adipokines, and participants not taking any medication ( n = 282, male/female: 126/156) were enrolled.…”

Section: Methodsmentioning

confidence: 99%

“…Concentrations of adiponectin, FABP4 and FGF21 were measured using enzyme‐linked immunosorbent assays kits for adiponectin (R&D Systems, Minneapolis, MN, USA), FABP4 (Biovendor, Modrice, Czech Republic) and FGF21 (R&D Systems), respectively. Variables of liver function, renal function, glucose and lipid metabolism were measured as previously described. Homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated as insulin (μU/mL) × glucose (mg/dL) / 405.…”

Section: Methodsmentioning

confidence: 99%

“…An accurate method for measuring plasma XOR activity in humans has recently been developed using liquid chromatography and triple quadrupole mass spectrometry. Using this method, we and others have recently shown that plasma XOR activity is independently associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance, suggesting that plasma XOR activity might be a new metabolic biomarker.…”

Section: Introductionmentioning

confidence: 99%

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Independent links between plasma xanthine oxidoreductase activity and levels of adipokines

Furuhashi

Matsumoto

Murase

et al. 2019

J of Diabetes Invest

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Aims/Introduction Xanthine oxidoreductase ( XOR ) is a rate‐limiting enzyme that catalyzes uric acid formation in the purine metabolism, is involved in an increase in reactive oxygen species. Plasma XOR activity has been shown to be associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance. Materials and Methods The association between plasma XOR activity, measured by using liquid chromatography and mass spectrometry, and levels of adipokines, including adiponectin, fatty acid‐binding protein 4 ( FABP 4) and fibroblast growth factor 21 ( FGF 21), was investigated in 282 participants (male/female: 126/156) of the Tanno‐Sobetsu Study who were not taking medication. Results Women had lower plasma XOR activity than did men. Smoking habit was associated with increased activity. Plasma XOR activity was positively correlated with concentrations of FABP 4 ( r = 0.192, P < 0.001) and FGF 21 ( r = 0.208, P < 0.001), homeostasis model assessment of insulin resistance as an index of insulin resistance and uric acid, and was negatively correlated with adiponectin level ( r = −0.243, P = 0.001). Multivariate regression analyses showed that levels of adiponectin, FABP 4 and FGF 21 were independent determinants of plasma XOR activity after adjusting age, sex, uric acid and homeostasis model assessment of insulin resistance. With additional adjustment of smoking habit, the level of FABP 4, but not that of adiponectin or FGF 21, remained as an independent predictor of plasma XOR activity. Conclusions Plasma XOR activity was independently associated with levels of adipokines in a general population of individuals not taking medication.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines

Furuhashi

Matsumoto

Murase

et al. 2019

J of Diabetes Invest

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“…Theoretically, XOR activity should be positively correlated with the serum UA levels because the production of UA requires activation of XOR. While the results of some recent studies support this hypothesis, 11,21,23 other studies report conflicting results. 9,10,22 Nevertheless, although XOR activity and serum UA levels were significantly correlated in the present study, the correlation coefficient was not definitive [r = 0.335 (Spearman), data not shown].…”

Section: Factors Associated With High Xanthine Oxidoreductase Activitmentioning

confidence: 94%

Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure requiring intensive care

et al. 2019

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Aims Plasma xanthine oxidoreductase (XOR) activity during the acute phase of acute heart failure (AHF) requires further elucidation. Methods and results One hundred eighteen AHF patients and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analysed. Blood samples were collected within 15 min of admission from AHF patients (AHF group) and control patients who visited a daily cardiovascular outpatient clinic (control group). Plasma XOR activity was compared between the two groups, and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the AHF group (median, 104.0 pmol/h/mL; range, 25.9–423.5 pmol/h/mL) was significantly higher than that in the control group (median, 45.2 pmol/h/mL; range, 19.3–98.8 pmol/h/mL). The multivariate logistic regression model showed that serum uric acid (per 1.0 mg/dL increase, odds ratio: 1.280; 95% confidence interval: 1.066–1.536; P = 0.008) and lactate levels (per 1.0 mmol/L increase, odds ratio: 1.239; 95% confidence interval: 1.040–1.475; P = 0.016) were independently associated with high plasma XOR activity (>300 pg/h/mL) during the acute phase of AHF. Conclusions Plasma XOR activity was extremely high in patients with severely decompensated AHF. This would be associated with a high lactate value and would eventually lead to hyperuricaemia in patients with AHF.

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Relationship Between Changing Body Mass Index and Serum Uric Acid Alteration Among Clinically Apparently Healthy Korean Men

Hwang

Lee

Ahn

et al. 2022

Arthritis Care & Research

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Objective. Gout and hyperuricemia incidence is increasing worldwide, reflecting pandemic overweight and obesity. However, the magnitude of the association of body mass index (BMI) changes with serum uric acid (UA) level in the general population has remained unevaluated.Methods. This retrospective cohort study enrolled 27,422 Korean men who underwent a comprehensive health check-up between 2015 and 2017. BMI change was categorized into 7 groups. The relationship between BMI change and serum UA level alteration was determined using multivariable regression models.Results. The mean age, BMI, and serum UA level were 38.8 years, 24.7 kg/m 2 , and 6.2 mg/dl, respectively. All BMI change categories had a clear dose-response relationship with the serum UA level changes. The corresponding β coefficient of serum UA level changes was 0.13 (95% confidence interval [95% CI] 0.11, 0.16), 0.25 (95% CI 0.2, 0.3), and 0.44 (95% CI 0.36, 0.52) for a BMI decrease of 0.5-1.5, 1.5-2.5, and ≥2.5, respectively. Compared with no BMI change, the multivariate odds ratios of achieving normouricemia for a BMI increase of 0.5-1.5, 1.5-2.5, and ≥2.5 were 0.88 (95% CI 0.83, 0.95), 0.67 (95% CI 0.60, 0.75), and 0.60 (95% CI 0.49, 0.74), whereas those for a BMI decrease of 0.

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Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population

Abstract: Plasma XOR activity is a novel biomarker of metabolic disorders in a general population.

Cited by 75 publications

References 42 publications

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines

Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure requiring intensive care

Relationship Between Changing Body Mass Index and Serum Uric Acid Alteration Among Clinically Apparently Healthy Korean Men

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