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.

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