High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB
Language: 
English
Abstract: 

BACKGROUND: Signal transducer and activator of transcription (Stat)-3 and nuclear factor-kappa B (NF-κB) are important signaling pathways constitutively activated during inflammation. We previously reported that high-fat diet (HFD) intake induces oxidative stress in the prostate through elevated expression of NADPH oxidase subunits causing NF-κB activation. We sought to determine whether Stat-3 is involved in the activation of NF-κB in the prostate as a result of HFD feeding, leading to inflammation. METHODS: C57BL/6 mice were either fed with regular diet (RD) or HFD for 4 and 8 weeks. Plasma cytokine levels were determined by multiplex analysis. Western blotting was performed to determine the expression of NF-κB, Stat-3, Akt, PDK1, PKCε, and their phosphorylated forms along with pathologic evaluation of the prostate. Immunoprecipitation and electrophoretic mobility shift assay (EMSA) were conducted to study the association between Stat-3 and NF-κB. RESULTS: C57BL/6 mice fed with HFD showed a significant increase in the plasma levels of IL-1ß, IL-6, IL-17, and TNFα after 4 and 8 weeks of feeding, compared with RD controls. HFD feeding elevated the intraprostatic expression of IL-6 and caused activation of PKCε and Akt, the upstream kinase regulating Stat-3 and NF-κB. Nuclear extracts from the prostates of mice fed with HFD exhibited constitutively activated levels of Stat-3 and NF-κB/p65. Increased association between the activated forms of Stat-3 and NF-κB/p65 was observed in the nucleus as a result of HFD feeding, a finding that was accompanied by morphologic evidence of increased intraprostatic inflammation. CONCLUSIONS: Our findings suggest that HFD activates Stat-3 and NF-κB/p65 in the prostate, and their interaction is associated with increased inflammation in the prostate.

Author(s): 
Shankar, Eswar
Vykhovanets, Eugene V.
Vykhovanets, Olena V.
Maclennan, Gregory T.
Singh, Rajesh
Bhaskaran, Natarajan
Shukla, Sanjeev
Gupta, Sanjay
Item Type: 
Journal Article
Publication Title: 
The Prostate
Journal Abbreviation: 
Prostate
Publication Date: 
Feb 2012
Publication Year: 
2012
Pages: 
233-243
Volume: 
72
Issue: 
3
ISSN: 
1097-0045
DOI: 
10.1002/pros.21425
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 21604287 PMCID: PMC3161175

Turabian/Chicago Citation

Eswar Shankar, Eugene V. Vykhovanets, Olena V. Vykhovanets, Gregory T. Maclennan, Rajesh Singh, Natarajan Bhaskaran, Sanjeev Shukla and Sanjay Gupta. Feb 2012. "High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB." The Prostate 72: 3: 233-243. 10.1002/pros.21425.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1002/pros.21425 | issn = 1097-0045 | volume = 72 | pages = 233-243 | last = Shankar | first = Eswar | coauthors = Vykhovanets, Eugene V., Vykhovanets, Olena V., Maclennan, Gregory T., Singh, Rajesh, Bhaskaran, Natarajan, Shukla, Sanjeev, Gupta, Sanjay | title = High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB | journal = The Prostate | date = Feb 2012 | pmid = | pmc = }} </ref>