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Cited by 337

The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.

Peroxisome Proliferator-activated Receptor α Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene

Open access
Barberá, M. José, Schlüter, Agatha, Pedraza, Neus, Iglesias, Roser, Villarroya, Francesc, Giralt, Marta·2001·Journal of Biological Chemistry

Abstract

High expression of the peroxisome proliferator-activated receptor alpha (PPARalpha) differentiates brown fat from white, and is related to its high capacity of lipid oxidation. We analyzed the effects of PPARalpha activation on expression of the brown fat-specific uncoupling protein-1 (ucp-1) gene. Activators of PPARalpha 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 PPARalpha co-transfection in a dose-dependent manner and this activation was potentiated by Wy 14,643 and retinoid X receptor alpha. The coactivators CBP and PPARgamma-coactivator-1 (PGC-1), which is highly expressed in brown fat, also enhanced the PPARalpha-dependent regulation of the ucp-1 gene. Deletion and point-mutation mapping analysis indicated that the PPARalpha-responsive element was located in the upstream enhancer region of the ucp-1 gene. This -2485/-2458 element bound PPARalpha and PPARgamma from brown fat nuclei. Moreover, this element behaved as a promiscuous responsive site to either PPARalpha or PPARgamma activation, and we propose that it mediates ucp-1 gene up-regulation associated with adipogenic differentiation (via PPARgamma) or in coordination with gene expression for the fatty acid oxidation machinery required for active thermogenesis (via PPARalpha).

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Metadata

Authors
Barberá, M. J., Schlüter, A., Pedraza, N., Iglesias, R., Villarroya, F., & Giralt, M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-01
Volume
276
Issue
2
Pages
1486-1493
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2096842458
Cited by
337
References
55
FWCI
2.93
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Peroxisome Proliferator-activated Receptor α Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene. https://app.cochat.ai/papers/10.1074/jbc.m006246200
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Barberá, M. J., Schlüter, A., Pedraza, N., Iglesias, R., Villarroya, F., & Giralt, M. (2001). Peroxisome Proliferator-activated Receptor α Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m006246200

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