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1 (PPAR1) and PPAR2 Messenger RNA Expression in the Early Stages of Adipogenesis1
Ligand Pharmaceuticals, Inc., San Diego, California 92121-3016 [R. S., S. D., M. B.]; Institut National de la Santé et de la Recherche Médicale U325 and Département d’Athérosclérose, Institut Pasteur de Lille, 59019 Lille, France [L. F., J. A.]; and Zen-Bio, Inc., Research Triangle Park, North Carolina 27709 [Y-D. H.]
Adipocyte differentiation is driven by the expression and activation of three transcription factor families: the differentially expressed CAAT/enhancer binding proteins (C/EBPs) 
, ß, and 
; the helix-loop-helix adipocyte differentiation and determination factor-1; and peroxisome proliferator activated receptor 
(PPAR), expressed as two isoforms, PPAR1 and the adipocyte-specific PPAR2. Overexpression of PPAR can induce adipocyte differentiation; therefore, we analyzed the expression of the two PPAR isoforms during early stages of differentiation to determine whether one was preferentially induced as an early determining event. Surprisingly, in the first 24 h, a 3–6-fold increase of PPAR2 mRNA was observed, whereas PPAR1 mRNA remained unchanged. PPAR1 was induced 1 day later. Overexpression of C/EBPß has also been shown to induce adipocyte differentiation. A C/EBP site was identified only in the human PPAR2 promoter. Its deletion blunted the response of PPAR2 promoter to cotransfected C/EBPß or methylisobutylxanthine treatment. We hypothesize that PPAR2 initiates adipocyte differentiation.
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| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
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