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http://hdl.handle.net/2445/108602
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DC Field | Value | Language |
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dc.contributor.author | García-Alonso, Verónica | - |
dc.contributor.author | López Vicario, Cristina | - |
dc.contributor.author | Titos Rodríguez, Esther | - |
dc.contributor.author | Morán-Salvador, Eva | - |
dc.contributor.author | González Périz, Ana | - |
dc.contributor.author | Rius, Bibiana | - |
dc.contributor.author | Párrizas, Marcelina | - |
dc.contributor.author | Werz, Oliver | - |
dc.contributor.author | Arroyo, Vicente | - |
dc.contributor.author | Clària i Enrich, Joan | - |
dc.date.accessioned | 2017-03-20T07:59:14Z | - |
dc.date.available | 2017-03-20T07:59:14Z | - |
dc.date.issued | 2013-08-13 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/2445/108602 | - |
dc.description.abstract | Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor and a master regulator of adipogenesis. Microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) is an inducible enzyme that couples with cyclooxygenase-2 for the biosynthesis of PGE2. In this study we demonstrate the existence of a coordinate functional interaction between PPARγ and mPGES-1 in controlling the process of pre-adipocyte differentiation in white adipose tissue (WAT). Adipocyte-specific PPARγ knock-out mice carrying an aP2 promoter-driven Cre recombinase transgene showed a blunted response to the adipogenic effects of a high fat diet. Pre-adipocytes from these knock-out mice showed loss of PPARγ and were resistant to rosiglitazone-induced WAT differentiation. In parallel, WAT from these mice showed increased expression of uncoupling protein 1, a mitochondrial enzyme that dissipates chemical energy as heat. Adipose tissue from mice lacking PPARγ also showed mPGES-1 up-regulation and increased PGE2 levels. In turn, PGE2 suppressed PPARγ expression and blocked rosiglitazone-induced pre-adipocyte differentiation toward white adipocytes while directly elevating uncoupling protein 1 expression and pre-adipocyte differentiation into mature beige/brite adipocytes. Consistently, pharmacological mPGES-1 inhibition directed pre-adipocyte differentiation toward white adipocytes while suppressing differentiation into beige/brite adipocytes. This browning effect was reproduced in knockdown experiments using a siRNA directed against mPGES-1. The effects of PGE2 on pre-adipocyte differentiation were not seen in mice lacking PPARγ in adipose tissue and were not mirrored by other eicosanoids (i.e. leukotriene B4). Taken together, these findings identify PGE2 as a key regulator of white-to-brown adipogenesis and suggest the existence of a coordinate regulation of adipogenesis between PPARγ and mPGES-1. | - |
dc.format.extent | 17 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M113.468603 | - |
dc.relation.ispartof | Journal of Biological Chemistry, 2013, vol. 288, num. 39, p. 28230-28242 | - |
dc.relation.uri | https://doi.org/10.1074/jbc.M113.468603 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2013 | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Teixit adipós | - |
dc.subject.classification | Prostaglandines | - |
dc.subject.classification | Trastorns del metabolisme | - |
dc.subject.classification | Regulació del metabolisme | - |
dc.subject.other | Adipose tissues | - |
dc.subject.other | Prostaglandins | - |
dc.subject.other | Disorders of metabolism | - |
dc.subject.other | Metabolic regulation | - |
dc.title | Coordinate Functional Regulation between Microsomal Prostaglandin E Synthase-1 (mPGES-1) and Peroxisome Proliferator-activated Receptor y (PPARy) in the Conversion of White-to-brown Adipocytes | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 627755 | - |
dc.date.updated | 2017-03-20T07:59:15Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 23943621 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) Articles publicats en revistes (Biomedicina) |
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File | Description | Size | Format | |
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627755.pdf | 2.56 MB | Adobe PDF | View/Open |
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