Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/102310
Title: Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis
Author: García-Alonso, Verónica
Titos Rodríguez, Esther
Alcaraz-Quiles, José
Rius, Bibiana
Lopategi, Aritz
López-Vicario, Cristina
Jakobsson, Per-Johan
Delgado, Salvadora
Lozano, Juanjo
Clària i Enrich, Joan
Keywords: Obesitat
Teixit adipós
Inflamació
Expressió gènica
Col·lagen
Obesity
Adipose tissues
Inflammation
Gene expression
Collagen
Issue Date: 28-Apr-2016
Publisher: Public Library of Science (PLoS)
Abstract: Obesity induces white adipose tissue (WAT) dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs) are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES). IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1) in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16) in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of interactions driving uncontrolled inflammation and fibrosis and impaired adaptive thermogenesis and lipolysis in human obese visceral WAT.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0153751
It is part of: PLoS One, 2016, vol. 11, num. 4, p. e0153751
Related resource: http://dx.doi.org/10.1371/journal.pone.0153751
URI: http://hdl.handle.net/2445/102310
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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