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.

Background Perivascular adipose tissue ( PVAT ) is causally associated with vascular function and the pathogenesis of vascular disease in association with metabolically driven chronic inflammation called metaflammation. However, the difference in PVAT surrounding the coronary artery ( CA ‐ PVAT ) and that surrounding the internal thoracic artery (ITA‐PVAT), a vessel resistant to atherosclerosis, remains unclear. Herein, we investigated whether CA ‐ PVAT , ITA ‐ PVAT , and subcutaneous adipose tissue ( SCAT ) have distinct phenotypes. Methods and Results Fat pads were sampled from 44 patients (men/women, 36:8; age, 67±13 years) with CA disease who underwent elective CA bypass grafting. Adipocyte size in ITA ‐ PVAT and that in CA ‐ PVAT were significantly smaller than that in SCAT . A greater extent of fibrosis and increased gene expression levels of fibrosis‐related molecules were observed in CA ‐ PVAT than those in SCAT and those in ITA ‐ PVAT . CA ‐ PVAT exhibited more pronounced metaflammation, as indicated by a significantly larger extent of CD 68‐positive and CD 11c‐positive M1 macrophages, a lower ratio of CD 206‐positive M2 to CD 11c‐positive M1 macrophages, a lower gene expression level of adiponectin, and higher gene expression levels of inflammatory cytokines and inflammasome‐ and endoplasmic reticulum stress–related molecules, than did ITA ‐ PVAT and SCAT . Expression patterns of adipocyte developmental and pattern‐forming genes were totally different among SCAT , ITA ‐ PVAT, and CA ‐ PVAT . Conclusions The phenotype of ITA ‐ PVAT is closer to that of SCAT than that of CA ‐ PVAT , which may result from inherent differences in adipocytes. ITA ‐ PVAT appears to be protected from metaflammation and consecutive adipose tissue remodeling, which may contribute to the decreased atherosclerotic plaque burden in the ITA.

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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