A Novel Splicing Variant of Peroxisome Proliferator-Activated Receptor-? (Ppar?1sv) Cooperatively Regulates Adipocyte Differentiation with Ppar?2.

ABSTRACT: 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 Ppar? (Ppar?1sv) that encodes PPAR?1 protein, and its importance in adipogenesis. The novel splicing variant has a unique 5'-UTR sequence, relative to those of Ppar?1 and Ppar?2 mRNAs, indicating the presence of a novel transcriptional initiation site and promoter for Ppar? expression. Ppar?1sv was highly expressed in the white and brown adipose tissues at levels comparable to Ppar?2. Ppar?1sv was synergistically up-regulated with Ppar?2 during adipocyte differentiation of 3T3-L1 cells and mouse primary cultured preadipocytes. Inhibition of Ppar?1sv by specific siRNAs completely abolished the induced adipogenesis in 3T3-L1 cells. C/EBP? and C/EBP? activated both the Ppar?1sv and Ppar?2 promoters in 3T3-L1 preadipocytes. These findings suggest that Ppar?1sv and Ppar?2 synergistically regulate the early stage of the adipocyte differentiation.

SUBMITTER: Takenaka Y 

PROVIDER: S-EPMC3686765 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature