title: Inflammatory Signaling Involved in High-Fat Diet Induced Prostate Diseases.
abstract: High-Fat Diet (HFD) has emerged as an important risk factor not only for obesity and diabetes but also for urological disorders. Recent research provides ample evidence that HFD is a putative cause for prostatic diseases including prostate cancer. The mechanisms whereby these diseases develop in the prostate have not been fully elucidated. In this review we discuss signaling pathways intricately involved in HFD-induced prostate disease. We performed a search through PUBMED using key words "high fat diet" and "prostate". Our data and perspectives are included in this review along with research performed by various other groups. HFD is positively associated with an increased risk of benign prostatic hyperplasia (BPH) and prostate cancer. HFD induces oxidative stress and inflammation in the prostate gland, and these adverse influences transform it from a normal to a diseased state. Studies demonstrate that HFD accelerates the generation of reactive oxygen species by driving the NADPH oxidase system, exacerbating oxidative stress in the prostate. HFD also causes a significant increase in the levels of pro-inflammatory cytokines and gene products through activation of two important signaling pathways: the Signal Transducer and Activator of Transcription (STAT)-3 and Nuclear Factor-kappa B (NF-κB). Both these pathways function as transcription factors required for regulating genes involved in proliferation, survival, angiogenesis, invasion and inflammation. The crosstalk between these two pathways enhances their regulatory function. Through its influences on the NF-κB and Stat-3 signaling pathways, it appears likely that HFD increases the risk of development of BPH and prostate cancer.
authors.affiliation: Department of Urology, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio 44106 USA.
authors.forename: Eswar
authors.initials: E
authors.lastname: Shankar
authors.affiliation: Department of Pathology, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, Ohio 44106 USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Bhaskaran
authors.affiliation: Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106 USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.affiliation: Case Comprehensive Cancer Center, Cleveland, Ohio 44106 USA.
authors.forename: Guiming
authors.initials: G
authors.lastname: Liu
authors.forename: Firouz
authors.initials: F
authors.lastname: Daneshgari
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
keywords: Benign prostatic hyperplasia; NADPH oxidase; Nuclear factor-kappa B; Signal transducer and activator of transcription; prostate cancer