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An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Endoplasmic reticulum stress regulates adipocyte resistin expression
Martina I Lefterova1, Shannon E Mullican, Takuya Tomaru
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Diabetes
|June 4, 2009
Summary
Endoplasmic reticulum (ER) stress reduces resistin mRNA and protein in mouse fat cells. This finding explains the paradoxical decrease in resistin gene expression observed in obesity.
Area of Science:
- Metabolic regulation
- Adipose tissue biology
- Endocrinology
Background:
- Resistin, a polypeptide hormone, impairs glucose metabolism and is primarily produced by adipocytes.
- Obesity in rodents is associated with elevated circulating resistin levels but paradoxically reduced adipose tissue resistin gene expression.
- The mechanism driving resistin mRNA downregulation in obesity remains unclear.
Purpose of the Study:
- To investigate the role of endoplasmic reticulum (ER) stress in regulating resistin expression in cultured mouse adipocytes.
- To elucidate the molecular mechanisms by which ER stress influences resistin gene expression.
Main Methods:
- Differentiated 3T3-L1 adipocytes were treated with ER stress inducers.
- Resistin mRNA and secreted protein levels were quantified.
- Expression and genomic binding of key transcriptional regulators (C/EBPα, PPARγ, CHOP10) were analyzed.
- Resistin mRNA levels and ER stress markers were assessed in adipose tissue from mice fed a high-fat diet.
Main Results:
- ER stress significantly reduced resistin mRNA and protein levels in 3T3-L1 adipocytes in a time- and dose-dependent manner.
- ER stress downregulated transcriptional activators (C/EBPα, PPARγ) and upregulated the repressor CHOP10, indicating transcriptional regulation of resistin.
- These findings were corroborated in adipose tissue from obese mice, showing a correlation between reduced resistin mRNA and ER stress.
Conclusions:
- Endoplasmic reticulum (ER) stress is a potent regulator of resistin expression at both mRNA and protein levels.
- ER stress likely underlies the local downregulation of resistin in adipose tissue during murine obesity.
- Elevated plasma resistin in obesity may stem from systemic factors rather than local adipose tissue production.
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