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 language | English |
|---|---|
| Pages (from-to) | 115-128 |
| Number of pages | 14 |
| Journal | Cell metabolism |
| Volume | 5 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 7 2007 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Molecular Biology
- Cell Biology
Cite this
Xanthine Oxidoreductase Is a Regulator of Adipogenesis and PPARγ Activity. / Cheung, Kevin J.; Tzameli, Iphigenia; Pissios, Pavlos; Rovira, Ilsa; Gavrilova, Oksana; Ohtsubo, Toshio; Chen, Zhu; Finkel, Toren; Flier, Jeffrey S.; Friedman, Jeffrey M.
In: Cell metabolism, Vol. 5, No. 2, 07.02.2007, p. 115-128.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Xanthine Oxidoreductase Is a Regulator of Adipogenesis and PPARγ Activity
AU - Cheung, Kevin J.
AU - Tzameli, Iphigenia
AU - Pissios, Pavlos
AU - Rovira, Ilsa
AU - Gavrilova, Oksana
AU - Ohtsubo, Toshio
AU - Chen, Zhu
AU - Finkel, Toren
AU - Flier, Jeffrey S.
AU - Friedman, Jeffrey M.
PY - 2007/2/7
Y1 - 2007/2/7
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33846684242&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2007.01.005
DO - 10.1016/j.cmet.2007.01.005
M3 - Article
C2 - 17276354
AN - SCOPUS:33846684242
VL - 5
SP - 115
EP - 128
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 2
ER -