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 e...

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Bibliographic Details
Published in:Cell 1995-12, Vol.83 (5), p.813-819
Main Authors: Kliewer, S A, Lenhard, J M, Willson, T M, Patel, I, Morris, D C, Lehmann, J M
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0092-8674
DOI:10.1016/0092-8674(95)90194-9