A Novel Splicing Variant of Peroxisome Proliferator- Activated Receptor-c (Pparc1sv) Cooperatively Regulates Adipocyte Differentiation with Pparc2

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate expression of a number of genes associated with the cellular differentiation and development. Here, we show the abundant and ubiquitous expression of a newly identified splicing variant of mouse Pparc (Pparc1sv) that encodes PPARc1 protein, and its importance in adipogenesis. The novel splicing variant has a unique 59-UTR sequence, relative to those of Pparc1 and Pparc2 mRNAs, indicating the presence of a novel transcriptional initiation site and promoter for Pparc expression. Pparc1sv was highly expressed in the white and brown adipose tissues at levels comparable to Pparc2. Pparc1sv was synergistically up-regulated with Pparc2 during adipocyte differentiation of 3T3-L1 cells and mouse primary cultured preadipocytes. Inhibition of Pparc1sv by specific siRNAs completely abolished the induced adipogenesis in 3T3-L1 cells. C/EBPb and C/EBPd activated both the Pparc1sv and Pparc2 promoters in 3T3-L1 preadipocytes. These findings suggest that Pparc1sv and Pparc2 synergistically regulate the early stage of the adipocyte differentiation