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

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 ga...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 1996-10, Vol.137 (10), p.4499-4502
Main Authors: Shalev, A, Siegrist-Kaiser, C A, Yen, P M, Wahli, W, Burger, A G, Chin, W W, Meier, C A
Format: Article
Language:English
Subjects:
Adipocytes
Immunoprecipitation
In vivo methods and tests
Insulin
Lipid metabolism
Lipids
Okadaic acid
Orthophosphate
Peroxisome proliferator-activated receptors
Phosphorylation
Receptors
Sensitizing
Thiazolidinediones
Thyroid
Time dependence
Transcription
Transfection
Vanadate
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Summary: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.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.137.10.8828512