Xanthine Oxidoreductase Is a Regulator of Adipogenesis and PPARγ Activity

Kevin J. Cheung, Iphigenia Tzameli, Pavlos Pissios, Ilsa Rovira, Oksana Gavrilova, Toshio Ohtsubo, Zhu Chen, Toren Finkel, Jeffrey S. Flier, Jeffrey M. Friedman

Research output: Contribution to journalArticle

Abstract

In an effort to identify novel candidate regulators of adipogenesis, gene profiling of differentiating 3T3-L1 preadipocytes was analyzed using a novel algorithm. We report here the characterization of xanthine oxidoreductase (XOR) as a novel regulator of adipogenesis. XOR lies downstream of C/EBPβ and upstream of PPARγ, in the cascade of factors that control adipogenesis, and it regulates PPARγ activity. In vitro, knockdown of XOR inhibits adipogenesis and PPARγ activity while constitutive overexpression increases activity of the PPARγ receptor in both adipocytes and preadipocytes. In vivo, XOR -/- mice demonstrate 50% reduction in adipose mass versus wild-type littermates while obese ob/ob mice exhibit increased concentrations of XOR mRNA and urate in the adipose tissue. We propose that XOR is a novel regulator of adipogenesis and of PPARγ activity and essential for the regulation of fat accretion. Our results identify XOR as a potential therapeutic target for metabolic abnormalities beyond hyperuricemia.

Original languageEnglish (US)
Pages (from-to)115-128
Number of pages14
JournalCell Metabolism
Volume5
Issue number2
DOIs
StatePublished - Feb 7 2007
Externally publishedYes

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Keywords

  • HUMDISEASE
  • SYSBIO

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Cheung, K. J., Tzameli, I., Pissios, P., Rovira, I., Gavrilova, O., Ohtsubo, T., Chen, Z., Finkel, T., Flier, J. S., & Friedman, J. M. (2007). Xanthine Oxidoreductase Is a Regulator of Adipogenesis and PPARγ Activity. Cell Metabolism, 5(2), 115-128. https://doi.org/10.1016/j.cmet.2007.01.005