You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 20131179 HIGH-FAT DIET INDUCED INFLAMMATION IN THE PROSTATE: ROLE OF STAT-3, ER-ALPHA AND AROMATASE Natarajan Bhaskaran, Sanjeev Shukla, Vijay Thakur, Melissa Babcook, Gregory MacLennan, Guiming Liu, Firouz Daneshgari, and Sanjay Gupta Natarajan BhaskaranNatarajan Bhaskaran Cleveland, OH More articles by this author , Sanjeev ShuklaSanjeev Shukla Cleveland, OH More articles by this author , Vijay ThakurVijay Thakur Cleveland, OH More articles by this author , Melissa BabcookMelissa Babcook Cleveland, OH More articles by this author , Gregory MacLennanGregory MacLennan Cleveland, OH More articles by this author , Guiming LiuGuiming Liu Cleveland, OH More articles by this author , Firouz DaneshgariFirouz Daneshgari Cleveland, OH More articles by this author , and Sanjay GuptaSanjay Gupta Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.816AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES High-fat diet (HFD), an unfortunate lifestyle choice common in the Western world, is associated with inflammation and thereby is regarded as a risk factor for obesity, diabetes, and cancer. The molecular mechanism(s) responsible for HFD-induced inflammation in the prostate gland are not well understood. Estrogen receptor alpha (ER-alpha), signal transducer and activator of transcription (Stat)-3 and aromatase are important signaling molecules constitutively activated in a setting of inflammation. We have previously reported that HFD activates a pro-inflammatory response in the prostate through elevated expression of Stat-3 (Prostate 72:233-43, 2012). In the current study, we sought to investigate a possible link between intraprostatic inflammation, HFD feeding, signaling molecules involved in inflammation (ER-alpha, Stat-3, p-Stat3 (Ser727) and aromatase). METHODS C57BL/6 mice were fed either a regular diet (RD) or a HFD for 4, 8 and 12 weeks. Serum, visceral fat and prostate tissues were obtained for analysis. Western blotting and immunohistochemistry (IHC) was performed to determine the expression of aromatase, ER-α, Stat-3 and its phosphorylated form along with pathologic evaluation of the prostate. Immunoprecipitation and ChIP were performed to study the association between aromatase, p-Stat-3 and ER-alpha. RESULTS HFD caused an increase in fat and serum testosterone levels. No significant changes were observed in the testosterone levels in the prostate. A marked increase in estrogen levels was noted in the prostate and visceral fat at 8 weeks of HFD intake. HFD feeding resulted in a significant increase in the expression of aromatase, ER-alpha, Stat-3 and p-Stat3 (Ser727) at the message and protein levels. Immunoprecipitation and ChIP analysis demonstrated an increased association between aromatase, p-Stat-3 and ER-alpha in the HFD group. IHC analysis revealed higher expression of Stat-3, ER-alpha and aromatase in the prostate, accompanied by the morphologic evidence of increased intraprostatic inflammation in the prostate of HFD group. CONCLUSIONS Our findings suggest that HFD increases estrogen levels by increased binding of ER-alpha and p-Stat-3 to the promoter of aromatase and their interaction is associated with increased intraprostatic inflammation. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e481 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Natarajan Bhaskaran Cleveland, OH More articles by this author Sanjeev Shukla Cleveland, OH More articles by this author Vijay Thakur Cleveland, OH More articles by this author Melissa Babcook Cleveland, OH More articles by this author Gregory MacLennan Cleveland, OH More articles by this author Guiming Liu Cleveland, OH More articles by this author Firouz Daneshgari Cleveland, OH More articles by this author Sanjay Gupta Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...