title: SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway.
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.
authors.affiliation: Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. zhuxiaoxia@medmail.com.cn.|Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China. zhuxiaoxia@medmail.com.cn.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Zhu
authors.affiliation: Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.|Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Rheumatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. hjzou@fudan.edu.cn.|Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12, Middle Wulumuqi Road, Shanghai, 200040, China. hjzou@fudan.edu.cn.
authors.forename: He-Jian
authors.initials: HJ
authors.lastname: Zou
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D033461:Hyperuricemia / Q000378:metabolism / Q000517:prevention & control*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D009363:Neoplasm Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D013267:Stilbenes; D014527:Uric Acid; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: ABCG2; Hyperuricemia; PGC-1α; PPARγ; SIRT1