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Títol:
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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
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Autor/a:
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García-Alonso, Verónica; López Vicario, Cristina; Titos Rodríguez, Esther; Morán-Salvador, Eva; González Périz, Ana; Rius, Bibiana; Párrizas, Marcelina; Werz, Oliver; Arroyo, Vicente; Clària i Enrich, Joan
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Notes:
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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. |
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Matèries:
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-Teixit adipós
-Prostaglandines
-Trastorns del metabolisme
-Regulació del metabolisme
-Adipose tissues
-Prostaglandins
-Disorders of metabolism
-Metabolic regulation |
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Drets:
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(c) American Society for Biochemistry and Molecular Biology, 2013
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Tipus de document:
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Article
Article - Versió publicada |
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Publicat per:
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American Society for Biochemistry and Molecular Biology
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Compartir:
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