title: A Novel Splicing Variant of Peroxisome Proliferator-Activated Receptor-γ (Pparγ1sv) Cooperatively Regulates Adipocyte Differentiation with Pparγ2.
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 Pparγ (Pparγ1sv) that encodes PPARγ1 protein, and its importance in adipogenesis. The novel splicing variant has a unique 5'-UTR sequence, relative to those of Pparγ1 and Pparγ2 mRNAs, indicating the presence of a novel transcriptional initiation site and promoter for Pparγ expression. Pparγ1sv was highly expressed in the white and brown adipose tissues at levels comparable to Pparγ2. Pparγ1sv was synergistically up-regulated with Pparγ2 during adipocyte differentiation of 3T3-L1 cells and mouse primary cultured preadipocytes. Inhibition of Pparγ1sv by specific siRNAs completely abolished the induced adipogenesis in 3T3-L1 cells. C/EBPβ and C/EBPδ activated both the Pparγ1sv and Pparγ2 promoters in 3T3-L1 preadipocytes. These findings suggest that Pparγ1sv and Pparγ2 synergistically regulate the early stage of the adipocyte differentiation.
authors.affiliation: Department of Diabetes and Endocrinology, Saitama Medical University, Saitama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takenaka
authors.forename: Ikuo
authors.initials: I
authors.lastname: Inoue
authors.forename: Takanari
authors.initials: T
authors.lastname: Nakano
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shinoda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
mesh_terms: D041721:3T3-L1 Cells; D020121:5' Untranslated Regions; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
chemical_list: D020121:5' Untranslated Regions; D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; C497253:Cebpd protein, mouse; D047495:PPAR gamma; D012333:RNA, Messenger; D051743:CCAAT-Enhancer-Binding Protein-delta