Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/27522
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | The peroxisome proliferator-activated receptor-γ regulates murine pyruvate carboxylase gene expression in vivo and in vitro |
Other Titles: | The peroxisome proliferator-activated receptor-gamma regulates murine pyruvate carboxylase gene expression in vivo and in vitro |
Author: | Jitrapakdee, S. Slawik, M. Medina-Gomez, G. Campbell, M. Wallace, J. Sethi, J. O'Rahilly, S. Vidal-Puig, A. |
Citation: | Journal of Biological Chemistry, 2005; 280(29):27466-27476 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2005 |
ISSN: | 0021-9258 |
Statement of Responsibility: | Sarawut Jitrapakdee, Marc Slawik, Gema Medina-Gomez, Mark Campbell, John C. Wallace, Jaswinder K. Sethi, Stephen O'Rahilly, and Antonio J. Vidal-Puig |
Abstract: | Pyruvate carboxylase (PC) plays a crucial role in various metabolic pathways, including gluconeogenesis, lipogenesis, and glucose-induced insulin secretion. Here we showed for the first time that the PC gene is transcriptionally regulated by peroxisome proliferator-activated receptor-γ (PPARγ) in vitro and in vivo in white and brown adipose tissue. PC mRNA and protein are markedly increased during differentiation of 3T3-L1 cells and HIB-1B, in parallel with the expression of the adipogenic transcription factors, CCAAT-enhancer binding protein α, PPARγ1, and PPARγ2. Tumor necrosis factor-α, a cytokine that blocks differentiation of 3T3-L1 cells, suppressed PC expression. Co-transfection studies in 3T3-L1 preadipocytes or HEK293T cells with a 2.3-kb promoter fragment of mouse PC gene linked to a luciferase reporter construct and with plasmids overexpressing retinoid X receptor /PPARγ1 or retinoid X receptor α/PPAR γ2 showed a 6-8-fold increase above the basal promoter activity. Furthermore, treatment of these transfected cells with the PPARγ agonist doubled the promoter activity. Mutation of the putative PPAR-response element-(-386/-374) of this 2.3-kb PC promoter fragment abolished the PPARγ response. Gel shift and chromatin immunoprecipitation assays demonstrated that endogenous PPARγ binds to this functional PPAR-response element of the PC promoter. Mice with targeted disruption of the PPARγ2 gene displayed ~50-60% reduction of PC mRNA and protein in white adipose tissue. Similarly, in brown adipose tissue of PPARγ2-deficient mice subjected to cold exposure, PC mRNA was 40% lower than that of wild type mice. Impaired in vitro differentiation of white adipocytes of PPARγ2 knock-out mice was also associated with a marked reduction of PC mRNA. Our findings identified PC as a PPAR γ-regulated gene and suggested a role for PPARγ regulating intermediary metabolism. |
Rights: | © 2005 by The American Society for Biochemistry and Molecular Biology |
DOI: | 10.1074/jbc.M503836200 |
Published version: | http://dx.doi.org/10.1074/jbc.m503836200 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.