Peroxisome Proliferator-Activated Receptor-γ Transcriptionally Up-Regulates Hormone-Sensitive Lipase via the Involvement of Specificity Protein-1 (original) (raw)
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Tuo Deng ,
1Department of Biological Science and Biotechnology (T.D., J.C.), Tsinghua University, Beijing 100084, China
2Chipscreen Biosciences Ltd. (T.D., S.S., X.-P.L., J.C., Z.-Q.N.), Shenzhen Research Institute of Tsinghua University, Shenzhen 518057, China
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2Chipscreen Biosciences Ltd. (T.D., S.S., X.-P.L., J.C., Z.-Q.N.), Shenzhen Research Institute of Tsinghua University, Shenzhen 518057, China
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3Institute of Materia Medica (P.-P.L., Z.-F.S.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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3Institute of Materia Medica (P.-P.L., Z.-F.S.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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2Chipscreen Biosciences Ltd. (T.D., S.S., X.-P.L., J.C., Z.-Q.N.), Shenzhen Research Institute of Tsinghua University, Shenzhen 518057, China
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1Department of Biological Science and Biotechnology (T.D., J.C.), Tsinghua University, Beijing 100084, China
2Chipscreen Biosciences Ltd. (T.D., S.S., X.-P.L., J.C., Z.-Q.N.), Shenzhen Research Institute of Tsinghua University, Shenzhen 518057, China
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2Chipscreen Biosciences Ltd. (T.D., S.S., X.-P.L., J.C., Z.-Q.N.), Shenzhen Research Institute of Tsinghua University, Shenzhen 518057, China
*Address all correspondence and requests for reprints to: Zhi-Qiang Ning, Chipscreen Biosciences Ltd., Shenzhen Research Institute of Tsinghua University, Nanshan District, Shenzhen 518057, China.
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Accepted:
24 October 2005
Published:
01 February 2006
Cite
Tuo Deng, Song Shan, Ping-Ping Li, Zhu-Fang Shen, Xian-Ping Lu, Jing Cheng, Zhi-Qiang Ning, Peroxisome Proliferator-Activated Receptor-γ Transcriptionally Up-Regulates Hormone-Sensitive Lipase via the Involvement of Specificity Protein-1, Endocrinology, Volume 147, Issue 2, 1 February 2006, Pages 875–884, https://doi.org/10.1210/en.2005-0623
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Both peroxisome proliferator-activated receptor (PPAR)-γ and hormone-sensitive lipase (HSL) play important roles in lipid metabolism and insulin sensitivity. We demonstrate that expression of the HSL gene is up-regulated by PPARγ and PPARγ agonists (rosiglitazone and pioglitazone) in the cultured hepatic cells and differentiating preadipocytes. Rosiglitazone treatment also results in up-regulation of the HSL gene in liver and skeleton muscle from an experimental obese rat model, accompanied by the decreased triglyceride content in these tissues. The proximal promoter (−87 bp of the human HSL gene) was found to be essential for PPARγ-mediated transactivating activity. This important promoter region contains two GC-boxes and binds the transcription factor specificity protein-1 (Sp1) but not PPARγ. The Sp1-promoter binding activity can be endogenously enhanced by PPARγ and rosiglitazone, as demonstrated by analysis of EMSA and chromatin immunoprecipitation assay. Mutations in the GC-box sequences reduce the promoter binding activity of Sp1 and the transactivating activity of PPARγ. In addition, mithramycin A, the specific inhibitor for Sp1-DNA binding activity, abolishes the PPARγ-mediated up-regulation of HSL. These results indicate that PPARγ positively regulates the HSL gene expression, and up-regulation of HSL by PPARγ requires the involvement of Sp1. Taken together, this study suggests that HSL may be a newly identified PPARγ target gene, and up-regulation of HSL may be an important mechanism involved in action of PPARγ agonists in type 2 diabetes.
Copyright © 2006 by The Endocrine Society
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