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Updated: Jun 24, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
The orphan nuclear receptor RORalpha restrains adipocyte differentiation through a reduction of C/EBPbeta activity
Nobumichi Ohoka1, Shogo Kato, Yu Takahashi
1Department of Applied Biological Chemistry, The University of Tokyo, Japan.
Abstract:
The nuclear receptor-type transcription factor retinoic acid receptor-related orphan receptor alpha (RORalpha) is a multifunctional molecule involved in tissue development and cellular function, such as inflammation, metabolism, and differentiation; however, the role of RORalpha during adipocyte differentiation has not yet been fully understood. Here we show that RORalpha inhibits the transcriptional activity of CCAAT/enhancer-binding protein beta (C/EBPbeta) without affecting its expression, thereby blocking the induction of both PPARgamma and C/EBPalpha, resulting in the suppression of C/EBPbeta-dependent adipogenesis. RORalpha interacted with C/EBPbeta so as to repress both the C/EBPbeta-p300 association and the C/EBPbeta-dependent recruitment of p300 to chromatin. In addition to the inhibitory effect on C/EBPbeta function, RORalpha also prevents the expression of the lipid droplet coating protein gene perilipin by peroxisome proliferators-activated receptor gamma (PPARgamma), acting through the specific mechanism of its promoter. We identified a suppressive ROR-responsive element overlapping the PPAR-responsive element in the perilipin promoter and verified that RORalpha competitively antagonizes the binding of PPARgamma. RORalpha inhibits PPARgamma-dependent adipogenesis along with the repression of perilipin induction. These findings suggest that RORalpha is a novel negative regulator of adipocyte differentiation that acts through dual mechanisms.
Insights
Retinoic acid receptor-related orphan receptor alpha (RORalpha) inhibits adipocyte differentiation by blocking key transcription factors. RORalpha negatively regulates adipogenesis through dual mechanisms, impacting C/EBPbeta and PPARgamma activity.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a transcription factor involved in various cellular functions.
- The precise role of RORalpha in adipocyte differentiation remains incompletely understood.
Purpose of the Study:
- To elucidate the role and mechanism of RORalpha in regulating adipocyte differentiation.
Main Methods:
- Investigated the interaction between RORalpha and CCAAT/enhancer-binding protein beta (C/EBPbeta).
- Assessed the impact of RORalpha on the expression of adipogenic genes like PPARgamma and C/EBPalpha.
- Analyzed the effect of RORalpha on perilipin gene expression and its promoter activity.
- Examined the competitive antagonism between RORalpha and peroxisome proliferators-activated receptor gamma (PPARgamma).
Main Results:
- RORalpha suppresses C/EBPbeta transcriptional activity, inhibiting C/EBPbeta-dependent adipogenesis.
- RORalpha represses the association of C/EBPbeta with p300 and its recruitment to chromatin.
- RORalpha antagonizes PPARgamma activity by binding to a suppressive ROR-responsive element in the perilipin promoter, thus inhibiting perilipin induction.
- RORalpha acts as a negative regulator of adipocyte differentiation through these dual mechanisms.
Conclusions:
- RORalpha is identified as a novel negative regulator of adipocyte differentiation.
- RORalpha inhibits adipogenesis by interfering with both C/EBPbeta and PPARgamma signaling pathways.
- These findings provide new insights into the molecular mechanisms controlling adipocyte development.
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