@article{3f788700ebbe11ddbf70000ea68e967b,
title = "Peroxisome proliferator-activated receptor delta (PPARdelta )-mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling",
abstract = "The peroxisome proliferator-activated receptor gamma (PPARgamma) is a key regulator of terminal adipocyte differentiation. PPARdelta is expressed in preadipocytes, but the importance of this PPAR subtype in adipogenesis has been a matter of debate. Here we present a critical evaluation of the role of PPARdelta in adipocyte differentiation. We demonstrate that treatment of NIH-3T3 fibroblasts overexpressing PPARdelta with standard adipogenic inducers led to induction of PPARgamma2 expression and terminal adipocyte differentiation in a manner that was strictly dependent on simultaneous administration of a PPARdelta ligand and methylisobutylxanthine (MIX) or other cAMP elevating agents. We further show that ligands and MIX synergistically stimulated PPARdelta-mediated transactivation. In 3T3-L1 preadipocytes, simultaneous administration of a PPARdelta-selective ligand and MIX significantly enhanced the early expression of PPARgamma and ALBP/aP2, but only modestly promoted terminal differentiation as determined by lipid accumulation. Finally, we provide evidence that synergistic activation of PPARdelta promotes mitotic clonal expansion in 3T3-L1 cells with or without forced expression of PPARdelta. In conclusion, our results suggest that PPARdelta may play a role in the proliferation of adipocyte precursor cells, whereas activation of endogenous PPARdelta in 3T3-L1 cells appears to have only minor impact on the processes leading to terminal adipocyte differentiation.",
author = "Hansen, {Jacob B.} and H Zhang and Rasmussen, {T H} and Petersen, {R K} and Flindt, {E N} and K Kristiansen",
note = "Keywords: 1-Methyl-3-isobutylxanthine; 3T3 Cells; Adipocytes; Animals; Cell Differentiation; Cell Division; Cyclic AMP; Gene Expression; Mice; Mitosis; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Transcription Factors; Transcriptional Activation",
year = "2001",
doi = "10.1074/jbc.M005567200",
language = "English",
volume = "276",
pages = "3175--82",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "5",
}