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Updated: Aug 14, 2026

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Protein inhibitor of activated STAT3 inhibits adipogenic gene expression
Jianbei Deng1, Kunjie Hua, Erica J Caveney
1Department of Nutrition, CB# 7461, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
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.
Insights
Protein inhibitor of activated STAT3 (PIAS3) inhibits adipogenesis by affecting insulin signaling. Increased PIAS3 in adipose tissue may contribute to obesity-related metabolic issues.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein inhibitor of activated STAT3 (PIAS3) is expressed in white adipose tissue.
- The role of PIAS3 in adipogenesis (fat cell formation) is currently unknown.
- PIAS3 is a repressor of signal transducer and activator of transcription 3 (STAT3).
Purpose of the Study:
- To investigate the role of PIAS3 in adipogenesis.
- To determine PIAS3's cellular localization and expression patterns during fat cell differentiation.
- To elucidate PIAS3's impact on key adipogenic gene expression and signaling pathways.
Main Methods:
- Studied PIAS3 expression and localization in 3T3-L1 cells during adipogenesis.
- Analyzed PIAS3 expression in white adipose tissue of ob/ob mice versus lean mice.
- Utilized PIAS3 overexpression in preadipocytes to assess effects on adipogenic gene expression and promoter activity.
Main Results:
- PIAS3 translocated from the nucleus to the cytoplasm during 3T3-L1 cell differentiation.
- PIAS3 expression was elevated in the white adipose tissue of obese mice.
- Overexpression of PIAS3 inhibited key adipogenic transcription factors (C/EBPalpha, PPARgamma) and downstream genes (aP2, adiponectin).
- PIAS3 specifically inhibited insulin-mediated C/EBPalpha promoter activation.
Conclusions:
- PIAS3 appears to inhibit adipogenesis by modulating insulin-activated transcription.
- Elevated PIAS3 in adipose tissue may contribute to metabolic disturbances associated with obesity.
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