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Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
Published on: March 28, 2013
PPARγ isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation.
D W Strand1, M Jiang, T A Murphy
1Department of Urologic Surgery, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Engineering, and Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA.
Cell Death & Disease
|August 10, 2012
Summary
PPARγ isoforms regulate prostate metabolism, shifting fuel use from glucose to fatty acids. PPARγ2 enhances differentiation, while PPARγ1 increases tumorigenicity, offering insights into metabolic diseases.
Area of Science:
- Metabolic regulation in prostate epithelial cells.
- Impact of Peroxisome proliferator-activated receptor gamma (PPARγ) on prostate health.
- Interplay between systemic metabolic dysfunction and prostatic diseases.
Background:
- Prostatic diseases are increasingly linked to systemic metabolic issues.
- Prostate-specific ablation of PPARγ in mice leads to tumorigenesis and autophagy.
- Fundamental questions remain about prostate metabolism.
Purpose of the Study:
- To investigate the distinct roles of individual PPARγ isoforms in regulating prostate epithelial cell metabolism.
- To understand how PPARγ isoforms influence lipogenesis, oxidative stress, and fuel utilization.
- To explore the impact of PPARγ isoforms on prostate cell differentiation and tumorigenicity.
Main Methods:
- Ectopic expression of PPARγ1 and PPARγ2 in PPARγ knockout prostate epithelial cells.
- Analysis of gene expression related to lipogenesis, oxidative stress, and fuel metabolism (e.g., Pdk4, Fabp4, Lpl, Acot1, Cd36).
- In vivo studies using PPARγ agonist and high-fat diet (HFD) in mice to confirm in vitro findings.
Main Results:
- Both PPARγ1 and PPARγ2 reduced de novo lipogenesis and oxidative stress, promoting a switch to fatty acid oxidation.
- PPARγ1 decreased cell differentiation and increased tumorigenicity, while upregulating Scd1 and triglyceride fatty acid desaturation.
- PPARγ2 increased basal cell differentiation, Scd1 expression, and androgen receptor (AR) expression and responsiveness.
- In vivo, PPARγ agonization increased prostate differentiation markers, whereas HFD downregulated PPARγ-regulated genes and decreased differentiation.
Conclusions:
- Individual PPARγ isoforms exert distinct control over prostate epithelial metabolism, differentiation, and tumorigenicity.
- PPARγ plays a crucial role in metabolic adaptation within the prostate, influencing glucose and fatty acid oxidation.
- These findings provide a basis for understanding metabolic alterations in benign and malignant prostatic diseases linked to metabolic stress.
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