A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation

S A Kliewer; J M Lenhard; T M Willson; I Patel; D C Morris; J M Lehmann

doi:10.1016/0092-8674(95)90194-9

A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation

Cell. 1995 Dec 1;83(5):813-9. doi: 10.1016/0092-8674(95)90194-9.

Authors

S A Kliewer¹, J M Lenhard, T M Willson, I Patel, D C Morris, J M Lehmann

Affiliation

¹ Department of Cell Biology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709, USA.

PMID: 8521498
DOI: 10.1016/0092-8674(95)90194-9

Abstract

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.

MeSH terms

Adipocytes / cytology*
Animals
Binding, Competitive
Cell Differentiation / drug effects
Cells, Cultured
Fibroblasts / cytology
Hypoglycemic Agents / pharmacology
Ligands
Mice
Microbodies / drug effects
Prostaglandin D2 / analogs & derivatives*
Prostaglandin D2 / metabolism
Prostaglandin D2 / pharmacology
Prostaglandins / metabolism
Prostaglandins / pharmacology
Pyrimidines / pharmacology
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
Recombinant Fusion Proteins / biosynthesis
Rosiglitazone
Signal Transduction / physiology
Thiazoles / pharmacology
Thiazolidinediones*
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptional Activation / drug effects*

Substances

15-deoxy-delta(12,14)-prostaglandin J2
Hypoglycemic Agents
Ligands
Prostaglandins
Pyrimidines
Receptors, Cytoplasmic and Nuclear
Recombinant Fusion Proteins
Thiazoles
Thiazolidinediones
Transcription Factors
Rosiglitazone
pirinixic acid
Prostaglandin D2
ciglitazone