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Updated: Jun 10, 2026
08:34
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
ATF3 negatively regulates adiponectin receptor 1 expression.
Hyun Jin Park1, Young Mi Kang, Cho Hee Kim
1Pusan National University, School of Korean Medicine, #30 Beom-eo ri, Mulguem-eup, Yangsan-si, Gyeongnam 609-735, South Korea.
Biochemical and Biophysical Research Communications
|August 11, 2010
Summary
The transcription factor ATF3 reduces adiponectin receptor 1 (AdipoR1) expression by binding to its promoter. This ATF3-mediated downregulation of AdipoR1 impairs adiponectin signaling and contributes to insulin resistance.
Area of Science:
- Endocrinology
- Molecular Biology
- Metabolic Syndrome
Background:
- Adiponectin is a hormone with antidiabetic and antiatherogenic properties.
- Adiponectin exerts its effects via AdipoR1 and AdipoR2 receptors.
- Regulation of AdipoR1 and AdipoR2 expression is not fully understood.
Purpose of the Study:
- To investigate the role of ATF3 in regulating AdipoR1 expression.
- To determine if ATF3 contributes to impaired adiponectin signaling.
Main Methods:
- Used endoplasmic reticulum (ER) stress inducer thapsigargin to assess AdipoR1 expression.
- Overexpressed ATF3 using lentivirus in various cell lines.
- Analyzed human AdipoR1 promoter activity and identified ATF3-binding sites.
- Performed chromatin immunoprecipitation (ChIP) assays to confirm ATF3 binding.
Main Results:
- ER stress and ATF3 overexpression decreased AdipoR1 expression.
- ATF3 directly binds to a specific region (-248 to -224) of the human AdipoR1 promoter.
- Deletion of the ATF3-binding site abolished ATF3-mediated repression of AdipoR1 promoter activity.
- ATF3 expression increased in conditions associated with decreased AdipoR1 expression (hyperglycemia, TNF-α).
Conclusions:
- ATF3 negatively regulates human AdipoR1 expression through direct promoter binding.
- ATF3-mediated downregulation of AdipoR1 contributes to the attenuation of adiponectin signaling.
- This mechanism plays a role in the induction of insulin resistance.
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