| First Author | García-Alonso V | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 39 | Pages | 28230-42 |
| PubMed ID | 23943621 | Mgi Jnum | J:203851 |
| Mgi Id | MGI:5528928 | Doi | 10.1074/jbc.M113.468603 |
| Citation | Garcia-Alonso V, et al. (2013) Coordinate functional regulation between microsomal prostaglandin E synthase-1 (mPGES-1) and peroxisome proliferator-activated receptor gamma (PPARgamma) in the conversion of white-to-brown adipocytes. J Biol Chem 288(39):28230-42 |
| abstractText | Peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma and mPGES-1 in controlling the process of pre-adipocyte differentiation in white adipose tissue (WAT). Adipocyte-specific PPARgamma 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 PPARgamma 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 PPARgamma also showed mPGES-1 up-regulation and increased PGE2 levels. In turn, PGE2 suppressed PPARgamma 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 PPARgamma 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 PPARgamma and mPGES-1. |
