TY - JOUR
T1 - Protein inhibitor of activated STAT3 inhibits adipogenic gene expression
AU - Deng, Jianbei
AU - Hua, Kunjie
AU - Caveney, Erica J.
AU - Takahashi, Nobuyuki
AU - Harp, Joyce B.
N1 - Funding Information:
This work was supported by US Public Health Service Grants DK53398 and DK59337. Adenoviruses containing GFP and FLAG-PIAS3 were generated by the UNC Center for Gastrointestinal Biology and Disease-Gene Therapy Center Virus Vector Core, DK34987. We thank the Gene Expression Core Facility at UNC-Chapel Hill for help with real-time (TaqMan) RT-PCR, and Dr. Craig Albright and Eric Klem for help with the indirect immunofluorescence study.
PY - 2006/1/20
Y1 - 2006/1/20
N2 - 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/EBPα and PPARγ, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBPα 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.
AB - 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/EBPα and PPARγ, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBPα 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.
KW - Adipogenesis
KW - C/EBPα
KW - Insulin
KW - PIAS3
KW - PPARγ
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U2 - 10.1016/j.bbrc.2005.10.217
DO - 10.1016/j.bbrc.2005.10.217
M3 - Article
C2 - 16329991
AN - SCOPUS:28844499004
VL - 339
SP - 923
EP - 931
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -