title: Protein inhibitor of activated STAT3 inhibits adipogenic gene expression.
abstract: Protein inhibitor of activated STAT3 (PIAS3), a cytokine-induced repressor of signal transducer and activator of transcription 3 (STAT3) and a modulator of a broad array of nuclear proteins, is expressed in white adipose tissue, but its role in adipogenesis is not known. Here, we determined that PIAS3 was constitutively expressed in 3T3-L1 cells at all stages of adipogenesis. However, it translocated from the nucleus to the cytoplasm 4 days after induction of differentiation by isobutylmethylxanthine, dexamethasone, and insulin (MDI). In ob/ob mice, PIAS3 expression was increased in white adipose tissue depots compared to lean mice and was found in the cytoplasm of adipocytes. Overexpression of PIAS3 in differentiating preadipocytes, which localized primarily to the nucleus, inhibited mRNA level gene expression of adipogenic transcription factors C/EBPalpha and PPARgamma, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBPalpha promoter activation mediated specifically by insulin, but not dexamethasone or isobutylmethylxanthine. Taken together, these data suggest that PIAS3 may play an inhibitory role in adipogenesis by modulating insulin-activated transcriptional activation events. Increased PIAS3 expression in adipose tissue may play a role in the metabolic disturbances of obesity.
authors.affiliation: Department of Nutrition, CB# 7461, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Jianbei
authors.initials: J
authors.lastname: Deng
authors.forename: Kunjie
authors.initials: K
authors.lastname: Hua
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Caveney
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Joyce B
authors.initials: JB
authors.lastname: Harp
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D007328:Insulin; D047495:PPAR gamma; C109279:Pias3 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011994:Recombinant Proteins