Journal of Biological Chemistry
Volume 288, Issue 38, 20 September 2013, Pages 27138-27149
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Metabolism
Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

https://doi.org/10.1074/jbc.M113.485094Get rights and content
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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.

Background: Purine metabolism in adipose tissue is largely unknown.

Results: Adipose tissue has abundant xanthine oxidoreductase activity. Uric acid is secreted from adipose tissues and cells, and the secretion is augmented in obese mice.

Conclusion: Adipose tissue can secrete uric acid in mice.

Significance: Dysfunction of obese adipose tissue could be related to overproduction of uric acid.

Adipocyte
Adipose Tissue Metabolism
Metabolic Diseases
Obesity
Uric Acid

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*

This work was supported in part by Grants-in-aid for Scientific Research (C) 24591351 (to H. N.) and 22590979 (to N. M.) and by Scientific Research on Innovative Areas Grant 22126008 (to T. F.). Tohru Funahashi is a member of the Department of Metabolism and Atherosclerosis, a sponsored course endowed by Kowa Co. Ltd. In this work, Osaka University's academia-industry collaboration policy positions the collaboration between Osaka University and Teijin Pharma Ltd.