Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight

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

doi:10.1507/endocrj.ej19-0053

Cited by 23 publications

(11 citation statements)

References 26 publications

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“…Together, these results suggest that XOR contributes to increase BP, at least in part via endothelial dysfunction through ROS production. Importantly, VFA (ρ = 0.513, p < 0.001) and HbA1c (ρ = 0.260, p = 0.001) were positively correlated with plasma XOR activity, which is consistent with previous reports including ours showing that obesity and glycemic control level are positively associated with plasma XOR activity 20,21 . Visceral fat accumulation and diabetes are known to be risk factors for development of hypertension, though the underlying mechanisms have yet to be fully elucidated.…”

Section: Discussionsupporting

confidence: 91%

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Yoshida

Kurajoh

Fukumoto

et al. 2020

Sci Rep

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Xanthine oxidoreductase (XoR) inhibitor administration reduces uric acid and reactive oxygen species (RoS) production, and also lowers blood pressure (Bp). However, the associations of plasma XoR activity, uric acid level, and oxidative stress levels with Bp remain unclear. this cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. plasma XoR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. Bp was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-RoMs) levels were simultaneously measured. Median plasma XoR activity, serum uric acid, d-RoMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XoR activity (β = 0.211, p = 0.019), but not serum uric acid (β = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-RoMs level, an independent association of plasma XoR activity with MAp was observed (β = 0.428, p = 0.001 and β = 0.019, p = 0.891, respectively; p for interaction = 0.046). XoR may contribute to the pathophysiology of higher Bp through RoS but not uric acid production, especially in patients with lower oxidative stress.

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Section: Discussionsupporting

confidence: 91%

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Yoshida

Kurajoh

Fukumoto

et al. 2020

Sci Rep

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“…To date, few studies have evaluated changes in the XOR activity. It was recently reported that, in a population‐based cohort, an annual change in plasma XOR activity was independently associated with a change in bodyweight, as well as that in liver enzymes 20 . In the present study, changes in bodyweight and BMI did not correlate with those in plasma XOR activity.…”

Section: Discussionmentioning

confidence: 99%

Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment

Kawachi

Fujishima

Nishizawa

et al. 2020

J of Diabetes Invest

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Aims/Introduction Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine and xanthine to xanthine and uric acid, respectively. Plasma XOR activity has recently been measured in humans. However, limited information is known about plasma XOR activity in patients with type 2 diabetes mellitus, and its changes after short‐term glycemic control treatment. Materials and Methods We enrolled 28 Japanese patients (10 men/18 women) with type 2 diabetes mellitus who were hospitalized to undergo medical treatment for diabetes. Plasma XOR activity, quantified using triple quadrupole mass spectrometry and liquid chromatography, and other clinical parameters were examined at admission and 2 weeks after treatment during hospitalization. Changes in plasma XOR activity after treatment during hospitalization and associated clinical parameters were assessed. Results At the time of admission, the median plasma XOR activity was 83.1 pmol/h/mL, with a wide range of 14.4–1150 pmol/h/mL. Multiple regression analysis identified serum aspartate transaminase and alanine transaminase levels as significant and independent factors correlating with the baseline plasma XOR. Two weeks of treatment during hospitalization was associated with a significant decrease in plasma XOR activity. Changes in serum aspartate transaminase were also the only significant and independent factor correlating with changes in plasma XOR activity. Conclusions A close relationship was observed between plasma XOR activity and liver transaminases in patients with type 2 diabetes mellitus, cross‐sectionally, and also across treatment during hospitalization.

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“…An accurate and sensitive assay for activity of plasma XOR in humans has been newly developed using liquid chromatography and triple quadrupole mass spectrometry to measure [ 13 C 2 , 15 N 2 ]‐uric acid using [ 13 C 2 , 15 N 2 ]‐xanthine as a substrate. Using this assay, we and others have shown that activity of plasma XOR is a novel metabolic biomarker associated with obesity, insulin resistance, hyperuricemia, liver dysfunction and adipokines. Furthermore, we showed unexpected high activity of plasma XOR in some hyperuricemic patients by using an XOR inhibitor and in some female relatively hypouricemic patients .…”

Section: Introductionmentioning

confidence: 86%

Differential regulation of hypoxanthine and xanthine by obesity in a general population

Furuhashi

Koyama

Higashiura

et al. 2020

J of Diabetes Invest

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Aims/Introduction: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. Materials and Methods: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study. Results: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. Conclusions: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.

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Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight

Cited by 23 publications

References 26 publications

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment

Differential regulation of hypoxanthine and xanthine by obesity in a general population

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