| First Author | Yu YH | Year | 2013 |
| Journal | J Lipid Res | Volume | 54 |
| Issue | 9 | Pages | 2391-9 |
| PubMed ID | 23821743 | Mgi Jnum | J:200769 |
| Mgi Id | MGI:5509250 | Doi | 10.1194/jlr.M037556 |
| Citation | Yu YH, et al. (2013) Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARgamma activity. J Lipid Res 54(9):2391-9 |
| abstractText | Adipocyte differentiation is a multistep program under regulation by several factors. Peroxisome proliferator-activated receptor gamma (PPARgamma) serves as a master regulator of adipogenesis. However, the endogenous ligand for PPARgamma remained elusive until 15-keto-PGE2 was identified recently as an endogenous PPARgamma ligand. In this study, we demonstrate that zinc-containing alcohol dehydrogenase 2 (ZADH2; here termed prostaglandin reductase-3, PTGR-3) is a new member of prostaglandin reductase family that converts 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2. Adipogenesis is accelerated when endogenous PTGR-3 is silenced in 3T3-L1 preadipocytes, whereas forced expression of PTGR-3 significantly decreases adipogenesis. PTGR-3 expression decreased during adipocyte differentiation, accompanied by an increased level of 15-keto-PGE2. 15-keto-PGE2 exerts a potent proadipogenic effect by enhancing PPARgamma activity, whereas overexpression of PTGR-3 in 3T3-L1 preadipocytes markedly suppressed the proadipogenic effect of 15-keto-PGE2 by repressing PPARgamma activity. Taken together, these findings demonstrate for the first time that PTGR-3 is a novel 15-oxoprostaglandin-Delta(13)-reductase and plays a critical role in modulation of normal adipocyte differentiation via regulation of PPARgamma activity. Thus, modulation of PTGR-3 might provide a novel avenue for treating obesity and related metabolic disorders. |
