title: Uric acid secretion from adipose tissue and its increase in obesity.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tsushima
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: hitoshin1127@endmet.med.osaka-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tochino
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Sekimoto
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nagao
authors.affiliation: Teijin Institute for Biomedical Research, Teijin Pharma Limited, Hino, Tokyo 191-8512, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shirakura
authors.affiliation: Teijin Institute for Biomedical Research, Teijin Pharma Limited, Hino, Tokyo 191-8512, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kato
authors.affiliation: Kondo Laboratory, Teijin Limited, Hino, Tokyo 191-8512, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Imaizumi
authors.affiliation: Teijin Institute for Biomedical Research, Teijin Pharma Limited, Hino, Tokyo 191-8512, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Teijin Institute for Biomedical Research, Teijin Pharma Limited, Hino, Tokyo 191-8512, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015687:Cell Hypoxia; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014527:Uric Acid / Q000378:metabolism*; D014968:Xanthine Dehydrogenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D014527:Uric Acid; D014968:Xanthine Dehydrogenase
keywords: Adipocyte; Adipose Tissue Metabolism; Metabolic Diseases; Obesity; Uric Acid
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