Peroxisome Proliferator-activated Receptor α Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene
| Autor: | Marta Giralt, Roser Iglesias, Agatha Schlüter, M. José Barberá, Francesc Villarroya, Neus Pedraza |
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| Rok vydání: | 2001 |
| Předmět: |
Regulation of gene expression
medicine.medical_specialty Adipose tissue Cell Biology Biology Retinoid X receptor Biochemistry Thermogenin Cell biology Endocrinology Lipid oxidation Adipogenesis Internal medicine Gene expression medicine Peroxisome proliferator-activated receptor alpha Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 276:1486-1493 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m006246200 |
| Popis: | High expression of the peroxisome proliferator-activated receptor α (PPARα) differentiates brown fat from white, and is related to its high capacity of lipid oxidation. We analyzed the effects of PPARα activation on expression of the brown fat-specific uncoupling protein-1 (ucp-1) gene. Activators of PPARα increased UCP-1 mRNA levels severalfold both in primary brown adipocytes and in brown fat in vivo. Transient transfection assays indicated that the (−4551)UCP1-CAT construct, containing the 5′-regulatory region of the rat ucp-1 gene, was activated by PPARα co-transfection in a dose-dependent manner and this activation was potentiated by Wy 14,643 and retinoid X receptor α. The coactivators CBP and PPARγ-coactivator-1 (PGC-1), which is highly expressed in brown fat, also enhanced the PPARα-dependent regulation of the ucp-1 gene. Deletion and point-mutation mapping analysis indicated that the PPARα-responsive element was located in the upstream enhancer region of the ucp-1 gene. This −2485/−2458 element bound PPARα and PPARγ from brown fat nuclei. Moreover, this element behaved as a promiscuous responsive site to either PPARα or PPARγ activation, and we propose that it mediates ucp-1 gene up-regulation associated with adipogenic differentiation (via PPARγ) or in coordination with gene expression for the fatty acid oxidation machinery required for active thermogenesis (via PPARα). |
| Databáze: | OpenAIRE |
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