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Keywords:

  • oxidative stress;
  • high-fat diet;
  • prostate;
  • obesity;
  • NF-κB

Abstract

BACKGROUND

High-fat diet (HFD) is considered as a major risk factor for benign prostatic diseases and cancer in the Western world. Studies have shown an association between oxidative stress and prostatic diseases. NF-κB has been implicated in stress response and is deregulated in prostrate disorders; therefore, we sought to determine whether HFD could induce oxidative stress in the prostate which could contribute to prostatic diseases.

METHODS

Transgenic NF-κB-Luc-Tag mice were either fed with regular diet (RD) or HFD for 12 weeks. Serial, non-invasive molecular imaging was performed to study NF-κB activation in the whole body, and in various organs including thymus, spleen, and prostate. Western blotting was used to determine the expression of NF-κB, its upstream and downstream targets in the prostate.

RESULTS

Twofold increase in whole body NF-κB activity in vivo and two to threefold upregulated prostate NF-κB activity ex vivo were observed after HFD intake compared with RD controls. HFD-induced NF-κB activity was elevated remarkably in the abdominal cavity, thymus, spleen, and prostate with increase in prostrate weight. In the prostrate, an increase in the protein expression of gp91phox, p22phox, and p47phox NADPH oxidase subunits was observed suggesting the involvement of HFD in causing oxidative stress. Nuclear extracts from the prostrate tissue showed an increased expression of p65/RelA that corresponded with elevated cytosolic levels of p-IκBα, along with increased expression of downstream targets of NF-κB, nitric oxide synthase, and cyclooxygenase-2.

CONCLUSIONS

Our findings suggest that HFD-mediated oxidative stress and deregulation of NADPH oxidase leads to NF-κB activation in the prostrate. Prostate 71: 147–156, 2011. © 2010 Wiley-Liss, Inc.