Open AccessDifferential regulation of hypoxanthine and xanthine by obesity in a general population
Author(s) -
Furuhashi Masato,
Koyama Masayuki,
Higashiura Yukimura,
Murase Takayo,
Nakamura Takashi,
Matsumoto Megumi,
Sakai Akiko,
Ohnishi Hirofumi,
Tanaka Marenao,
Saitoh Shigeyuki,
Moniwa Norihito,
Shimamoto Kazuaki,
Miura Tetsuji
Publication year - 2020
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.13207
Subject(s) - hypoxanthine , hyperuricemia , xanthine , uric acid , medicine , endocrinology , obesity , xanthine oxidase , population , aspartate transaminase , xanthine dehydrogenase , body mass index , insulin resistance , chemistry , biochemistry , enzyme , environmental health , alkaline phosphatase
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.