PPARgamma ligand-dependent induction of STAT1, STAT5A, and STAT5B during adipogenesis.
We have recently demonstrated that STAT1, STAT5A, and STAT5B are induced during adipogenesis of cultured preadipocytes in a differentiation-dependent manner. Members of the C/EBP and PPAR families of transcription factors have also been shown to be induced during adipocyte differentiation and to play a significant role in the regulation of fat-specific genes. In this investigation, we have examined the ability of C/EBPs and PPARs to contribute to STAT protein expression during conversion of non-precursor fibroblasts to functionally mature adipocytes. For this study, NIH-3T3 fibroblasts engineered to ectopically co-express C/EBPbeta and C/EBPdelta under the control of a tetracycline-responsive, inducible expression system were utilized to assess STAT expression during controlled adipogenesis. Data presented here demonstrate that STAT1, STAT5A, and STAT5B, but not STAT3 and STAT6, were induced in a tetracycline-responsive manner during the differentiation of these engineered fibroblasts. The STAT protein accumulation resulting from C/EBP expression was tightly coupled to the morphological conversion of fibroblasts to adipocytes and represents an expression profile identical to that reported for mature adipocytes in vivo. Data are also presented demonstrating that STAT protein accumulation and adipocyte conversion occurred only during controlled conditions leading to the expression of PPARgamma and that the expression of these three STATs was tightly regulated in a PPARgamma ligand dose-response fashion. These data illustrate that the cascade of transcriptional events leading to adipogenesis regulate the STAT family of transcription factors and that the differentiation-dependent upregulation of STAT protein expression is regulated downstream of PPARgamma in a ligand-dependent manner.
Stephens
J M
JM
Department of Biological Sciences, Louisiana State University, Life Sciences Building, Room 508, Baton Rouge, Louisiana 70803, USA. jsteph1@unix1.snce.lsu.edu
Morrison
R F
RF
Wu
Z
Z
Farmer
S R
SR
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D008024:Ligands; D050356:Lipid Metabolism; D051379:Mice; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; D008894:Milk Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D013752:Tetracycline