Independent links between plasma xanthine oxidoreductase activity and levels of adipokines

Abstract

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.

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

“…Change in body weight may be indirectly associated with change in plasma XOR activity through modulation of hypoxanthine secretion from adipose tissue as a substrate of XOR. Other than liver dysfunction and obesity, plasma activity of XOR is associated with a habit of smoking and the presence of lifestyle-related diseases, including hyperuricemia, hypertension, dyslipidemia and diabetes mellitus [6][7][8][9]. However, in the present study, no significant difference was observed between annual changes in plasma XOR activities in participants with and those without a habit of smoking (Fig.…”

“…An accurate assay for plasma activity of XOR in humans has recently been established using triple quadrupole mass spectrometry and liquid chromatography to detect the formation of [ 13 C 2 , 15 [5]. Using this method, we and others have recently demonstrated that plasma XOR activity is a new biomarker of metabolic disorders associated with obesity, insulin resistance, liver dysfunction, hyperuricemia and adipokines [6][7][8][9]. In addition, it has been reported that habitual exercise can decrease plasma XOR activity [10].…”

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

“…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 .…”

Association between circulating fibroblast growth factor 21, aerobic fitness, and aortic blood pressure in middle-aged and older women

“…FGF21, fibroblast growth factor 21. Circulating FGF21 levels have been reported being related to several risk factors of cardiovascular disease (e.g., increase in blood lipid and glucose 12) , oxidative stress 26) , and inflammation 27) ) and to be higher in hypertensive adults than healthy adults 11) . The present study demonstrated, in middle-aged and older women without hypertension, that serum FGF21 levels were independently associated with aortic BP, particularly aortic PP which is more strongly associated with the risk of cardiovascular disease than peripheral BP 28,29) .…”