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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 | 2017-03-20T07:59:14Z |
dc.date | 2017-03-20T07:59:14Z |
dc.date | 2013-08-13 |
dc.date | 2017-03-20T07:59:15Z |
dc.identifier | 0021-9258 |
dc.identifier | 627755 |
dc.identifier | 23943621 |
dc.identifier.uri | http://hdl.handle.net/2445/108602 |
dc.description | 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 | 17 p. |
dc.format | application/pdf |
dc.language | eng |
dc.publisher | American Society for Biochemistry and Molecular Biology |
dc.relation | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M113.468603 |
dc.relation | Journal of Biological Chemistry, 2013, vol. 288, num. 39, p. 28230-28242 |
dc.relation | https://doi.org/10.1074/jbc.M113.468603 |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2013 |
dc.rights | info:eu-repo/semantics/openAccess |
dc.subject | Teixit adipós |
dc.subject | Prostaglandines |
dc.subject | Trastorns del metabolisme |
dc.subject | Regulació del metabolisme |
dc.subject | Adipose tissues |
dc.subject | Prostaglandins |
dc.subject | Disorders of metabolism |
dc.subject | 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 |