| First Author | Strand DW | Year | 2012 |
| Journal | Cell Death Dis | Volume | 3 |
| Pages | e361 | PubMed ID | 22874998 |
| Mgi Jnum | J:300447 | Mgi Id | MGI:6471182 |
| Doi | 10.1038/cddis.2012.99 | Citation | Strand DW, et al. (2012) PPARgamma isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation. Cell Death Dis 3:e361 |
| abstractText | Recent observations indicate prostatic diseases are comorbidities of systemic metabolic dysfunction. These discoveries revealed fundamental questions regarding the nature of prostate metabolism. We previously showed that prostate-specific ablation of PPARgamma in mice resulted in tumorigenesis and active autophagy. Here, we demonstrate control of overlapping and distinct aspects of prostate epithelial metabolism by ectopic expression of individual PPARgamma isoforms in PPARgamma knockout prostate epithelial cells. Expression and activation of either PPARgamma 1 or 2 reduced de novo lipogenesis and oxidative stress and mediated a switch from glucose to fatty acid oxidation through regulation of genes including Pdk4, Fabp4, Lpl, Acot1 and Cd36. Differential effects of PPARgamma isoforms included decreased basal cell differentiation, Scd1 expression and triglyceride fatty acid desaturation and increased tumorigenicity by PPARgamma1. In contrast, PPARgamma2 expression significantly increased basal cell differentiation, Scd1 expression and AR expression and responsiveness. Finally, in confirmation of in vitro data, a PPARgamma agonist versus high-fat diet (HFD) regimen in vivo confirmed that PPARgamma agonization increased prostatic differentiation markers, whereas HFD downregulated PPARgamma-regulated genes and decreased prostate differentiation. These data provide a rationale for pursuing a fundamental metabolic understanding of changes to glucose and fatty acid metabolism in benign and malignant prostatic diseases associated with systemic metabolic stress. |
