The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin.


Journal Article

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily implicated in adipocyte differentiation. The observations that PPAR alpha is a regulator of hepatic lipid metabolism and that the insulin-sensitizing thiazolidinediones are ligands for PPAR gamma suggest that cross-talk might exist between insulin signaling and PPAR activity, possibly through insulin-induced PPAR phosphorylation. Immunoprecipitation of endogenous PPAR alpha from primary rat adipocytes prelabeled with [32P]-orthophosphate and pretreated for 2 h with vanadate and okadaic acid demonstrated for the first time that PPAR alpha is a phosphoprotein in vivo. Treatment with insulin induced a time-dependent increase in PPAR phosphorylation showing a 3-fold increase after 30 min. Insulin also increased the phosphorylation of human PPAR alpha expressed in CV-1 cells. These changes in phosphorylation were paralleled by enhanced transcriptional activity of PPAR alpha and gamma. Transfection studies in CV-1 cells and HepG2 cells revealed a nearly 2-fold increase of PPAR activity in the presence of insulin. In contrast, insulin had no effect on the transcriptional activity of transfected thyroid hormone receptor in CV-1 cells, suggesting a PPAR-specific effect. Thus, insulin stimulates PPAR alpha phosphorylation and enhances the transcriptional activity of PPAR, suggesting that the transcriptional activity of this nuclear hormone receptor might be modulated by insulin-mediated phosphorylation.

Full Text

Duke Authors

Cited Authors

  • Shalev, A; Siegrist-Kaiser, CA; Yen, PM; Wahli, W; Burger, AG; Chin, WW; Meier, CA

Published Date

  • October 1996

Published In

Volume / Issue

  • 137 / 10

Start / End Page

  • 4499 - 4502

PubMed ID

  • 8828512

Pubmed Central ID

  • 8828512

International Standard Serial Number (ISSN)

  • 0013-7227

Digital Object Identifier (DOI)

  • 10.1210/endo.137.10.8828512


  • eng

Conference Location

  • United States