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

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.

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: 
Publication Date: 
Feb 2012
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
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>