Hirofumi Nagao1, Hitoshi Nishizawa1, Yoshimitsu Tanaka1, Tadafumi Fukata2, Tsunekazu Mizushima2, Masahiro Furuno3, Takeshi Bamba3,4, Yu Tsushima5, Yuya Fujishima1, Shunbun Kita1,6, Tohru Funahashi1,6, Norikazu Maeda1,6, Masaki Mori2, Eiichiro Fukusaki3, Iichiro Shimomura1. 1. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 2. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 3. Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan. 4. Division of Metabolomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. 5. Teijin Institute for Bio-medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan. 6. Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Abstract
OBJECTIVE: The production of uric acid in murine white adipose tissue (mWAT), and that such production was augmented in obese mice, was recently reported. However, little is known about the secretion of metabolites associated with purine catabolism in human WAT (hWAT). The present study analyzed this in hWAT. METHODS: Freshly isolated hWAT and mWAT were cultured. The secretion of metabolites associated with purine catabolism was measured. Tissue distribution profiles of genes associated with purine metabolism and metabolite profiling of adipocytes in hypoxia were analyzed. RESULTS: Secretion of hypoxanthine from hWAT was higher than those of xanthine and uric acid. On the other hand, secretion of uric acid was relatively higher than xanthine and hypoxanthine in mWAT. Xanthine oxidoreductase (XOR) mRNA expression levels in hWAT were markedly lower than that in the human liver. In murine tissues, XOR mRNA expression levels in mWAT were comparable with those in the liver. Cultured human adipocytes secreted hypoxanthine, and its secretion was increased under hypoxia. The metabolic analysis of human adipocytes showed that hypoxia increased metabolites associated with de novo biosynthesis of purine nucleotides. CONCLUSIONS: The present study revealed that hypoxanthine was secreted from human adipose tissue, and the secretion might be increased in local hypoxia.
OBJECTIVE: The production of uric acid in murine white adipose tissue (mWAT), and that such production was augmented in obesemice, was recently reported. However, little is known about the secretion of metabolites associated with purine catabolism in human WAT (hWAT). The present study analyzed this in hWAT. METHODS: Freshly isolated hWAT and mWAT were cultured. The secretion of metabolites associated with purine catabolism was measured. Tissue distribution profiles of genes associated with purine metabolism and metabolite profiling of adipocytes in hypoxia were analyzed. RESULTS: Secretion of hypoxanthine from hWAT was higher than those of xanthine and uric acid. On the other hand, secretion of uric acid was relatively higher than xanthine and hypoxanthine in mWAT. Xanthine oxidoreductase (XOR) mRNA expression levels in hWAT were markedly lower than that in the human liver. In murine tissues, XOR mRNA expression levels in mWAT were comparable with those in the liver. Cultured human adipocytes secreted hypoxanthine, and its secretion was increased under hypoxia. The metabolic analysis of human adipocytes showed that hypoxia increased metabolites associated with de novo biosynthesis of purine nucleotides. CONCLUSIONS: The present study revealed that hypoxanthine was secreted from humanadipose tissue, and the secretion might be increased in local hypoxia.
Authors: Hannah J Irvine; Animesh Acharjee; Zoe Wolcott; Zsuzsanna Ament; H E Hinson; Bradley J Molyneaux; J Marc Simard; Kevin N Sheth; W Taylor Kimberly Journal: Cell Rep Med Date: 2022-06-13
Authors: Cyrielle Doigneaux; Anthony M Pedley; Ishna N Mistry; Monika Papayova; Stephen J Benkovic; Ali Tavassoli Journal: J Biol Chem Date: 2020-05-21 Impact factor: 5.157