A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation.
Prostaglandins (PGs) of the J2 series form in vivo and exert effects on a variety of biological processes. While most of PGs mediate their effects through G protein-coupled receptors, the mechanism of action for the J2 series of PGs remains unclear. Here, we report the PGJ2 and its derivatives are efficacious activators of peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation. The PGJ2 metabolite 15-deoxy-delta 12,14-PGJ2 binds directly to PPAR gamma and promotes efficient differentiation of C3H10T1/2 fibroblasts to adipocytes. These data provide strong evidence that a fatty acid metabolite can function as an adipogenic agent through direct interactions with PPAR gamma and furthermore, suggest a novel mechanism of action for PGs of the J2 series.
Kliewer
S A
SA
Department of Cell Biology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709, USA.
Lenhard
J M
JM
Willson
T M
TM
Patel
I
I
Morris
D C
DC
Lehmann
J M
JM
D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008830:Microbodies / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007004:Hypoglycemic Agents; D008024:Ligands; D011453:Prostaglandins; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; C006253:pirinixic acid; D015230:Prostaglandin D2; C039671:ciglitazone