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01-08-2016 | Original Article

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

Authors: Juan Wang, Xiao-Xia Zhu, Lei Liu, Yu Xue, Xue Yang, He-Jian Zou

Published in: Endocrine | Issue 2/2016

Abstract

Silent information regulator T1 (SIRT1) plays several key roles in the regulation of lipid and glucose homoeostasis. In this study, we investigated the potential role of SIRT1 in hyperuricemia and explored possible mechanisms. Significant hyperuricemia was detected in C57BL/6 mice treated with oxonate and yeast polysaccharide. Resveratrol (RSV), a specific SIRT1 activator, was administered to the mice. SIRT1 suppressed the increased serum uric acid level but up-regulated the expression of urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the ileum of hyperuricemic mice. In a human colon carcinoma cell line, SIRT1 promoted ABCG2 production through the deacetylation of peroxisome proliferator-activated receptor (PPAR) γ co-activator 1α (PGC-1α), which then activated the effectors of PPARγ. Interestingly, the SIRT1-induced up-regulation of ABCG2 was significantly inhibited when PGC-1α or PPARγ was blocked by siRNA transfection. Our data demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. One possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway.

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Title: SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway
Authors: Juan Wang
Xiao-Xia Zhu
Lei Liu
Yu Xue
Xue Yang
He-Jian Zou
Publication date: 01-08-2016
Publisher: Springer US
Published in: Endocrine / Issue 2/2016
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-016-0896-7

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