Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of PPARγ activity
Journal
Journal of Lipid Research
Journal Volume
54
Journal Issue
9
Pages
2391-2399
Date Issued
2013
Author(s)
Abstract
Adipocyte differentiation is a multistep program under regulation by several factors. Peroxisome proliferator- activated receptor γ (PPARγ ) serves as a master regulator of adipogenesis. However, the endogenous ligand for PPARγ remained elusive until 15-keto-PGE2 was identified recently as an endogenous PPARγ 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-PGE 2. 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 PPARγ activity, whereas overexpression of PTGR-3 in 3T3-L1 preadipocytes markedly suppressed the proadipogenic effect of 15-keto-PGE2 by repressing PPARγ activity. Taken together, these findings demonstrate for the first time that PTGR-3 is a novel 15-oxoprostaglandin-Δ13- reductase and plays a critical role in modulation of normal adipocyte differentiation via regulation of PPARγ activity. Thus, modulation of PTGR-3 might provide a novel avenue for treating obesity and related metabolic disorders. Copyright ? 2013 by the American Society for Biochemistry and Molecular Biology, Inc.
SDGs
Other Subjects
13,14 dihydro 15 keto prostaglandin E2; 15 keto prostaglandin E2; 15 oxoprostaglandin 13 reductase; oxidoreductase; peroxisome proliferator activated receptor gamma; prostaglandin E2 derivative; prostaglandin reductase 3; unclassified drug; adipogenesis; article; cell differentiation; cell level; cell strain 3T3; controlled study; enzyme regulation; gene silencing; in vitro study; metabolic disorder; mitosis inhibition; priority journal; proadipocyte; protein expression; protein family; protein function; receptor upregulation; transient transfection; adipocyte differentiation; eicosanoid; ligand; nuclear receptor; Adipocytes; Adipogenesis; Adipose Tissue, White; Adiposity; Animals; Cell Line; Dinoprostone; Mice; Obesity; Oxidoreductases Acting on CH-CH Group Donors; PPAR gamma
Type
journal article