Rosiglitazone Induces Mitochondrial Biogenesis in Differentiated Murine 3T3-L1 and C3H/10T1/2 Adipocytes

被引:34
作者
Rong, James X. [1 ]
Klein, Jean-Louis D. [1 ]
Qiu, Yang [2 ]
Xie, Mi [1 ]
Johnson, Jennifer H. [1 ]
Waters, K. Michelle [1 ]
Zhang, Vivian [3 ]
Kashatus, Jennifer A. [1 ]
Remlinger, Katja S. [4 ]
Bing, Nan [2 ]
Crosby, Renae M. [1 ]
Jackson, Tymissha K. [1 ]
Witherspoon, Sam M. [1 ]
Moore, John T. [1 ]
Ryan, Terence E. [5 ]
Neill, Sue D. [1 ]
Strum, Jay C. [1 ]
机构
[1] GlaxoSmithKline, Mol Discovery Res, Metab Discovery Technol Grp, Res Triangle Pk, NC 27709 USA
[2] GlaxoSmithKline, Mol Discovery Res, Cheminformat, Res Triangle Pk, NC 27709 USA
[3] GlaxoSmithKline, Mol Discovery Res, Oncol Discovery Technol Grp, King Of Prussia, PA 19406 USA
[4] GlaxoSmithKline, Discovery Analyt, Res Triangle Pk, NC 27709 USA
[5] GlaxoSmithKline, Discovery Res, Integrat Biol, High Throughput Biol, King Of Prussia, PA 19406 USA
关键词
ACTIVATED RECEPTOR-GAMMA; MOUSE EMBRYO CELLS; GENE-EXPRESSION; PROTEIN-1; GENE; PRIMARY TARGET; ADIPOSE; PPAR; MECHANISMS; RIP140; ADIPOGENESIS;
D O I
10.1155/2011/179454
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Growing evidence indicates that PPAR. agonists, including rosiglitazone (RSG), induce adipose mitochondrial biogenesis. By systematically analyzing mitochondrial gene expression in two common murine adipocyte models, the current study aimed to further establish the direct role of RSG and capture temporal changes in gene transcription. Microarray profiling revealed that in fully differentiated 3T3-L1 and C3H/10T1/2 adipocytes treated with RSG or DMSO vehicle for 1, 2, 4, 7, 24, and 48 hrs, RSG overwhelmingly increased mitochondrial gene transcripts time dependently. The timing of the increases was consistent with the cascade of organelle biogenesis, that is, initiated by induction of transcription factor(s), followed by increases in the biosynthesis machinery, and then by increases in functional components. The transcriptional increases were further validated by increased mitochondrial staining, citrate synthase activity, and O-2 consumption, and were found to be associated with increased adiponectin secretion. The work provided further insight on the mechanism of PPAR gamma-induced mitochondrial biogenesis in differentiated adipocytes.
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页数:11
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