Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Teijin Institute for Biomedical Research, Teijin Pharma Limited, Hino, Tokyo 191-8512, Japan.
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
J Biol Chem. 2013 Sep 20;288(38):27138-27149. doi: 10.1074/jbc.M113.485094. Epub 2013 Aug 2.
Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity.
肥胖常伴有高尿酸血症。然而，嘌呤在各种组织中的代谢，尤其是尿酸生成，尚未被完全阐明。在这里，我们利用小鼠模型报告称，脂肪组织可以通过黄嘌呤氧化还原酶（XOR）产生和分泌尿酸，并且在肥胖时这种产生会增强。肥胖小鼠的血浆尿酸水平升高，而 XOR 抑制剂非布司他的给药可使其降低。脂肪组织是具有丰富 XOR 表达和活性的主要器官之一，肥胖小鼠的脂肪组织 XOR 活性高于对照组小鼠。3T3-L1 和小鼠原代成熟脂肪细胞可将尿酸产生和分泌到培养基中。尿酸的分泌可被非布司他剂量依赖性抑制或通过 XOR 的基因敲低抑制。脂肪组织的手术缺血通过 XOR 增加局部尿酸生成和分泌，随后循环尿酸水平升高。肥胖小鼠的整个脂肪组织尿酸分泌增加，3T3-L1 脂肪细胞在缺氧条件下的尿酸分泌增加。我们的结果表明，肥胖时脂肪组织中的嘌呤分解代谢可能增强。
