title: Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.
abstract: BACKGROUND
  BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association.
  
  
  METHODS
  Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI).
  
  
  RESULTS
  Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation.
  
  
  CONCLUSIONS
  The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.
authors.affiliation: Departments of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Fowke
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Pathology, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
mesh_terms: D000368:Aged; D015415:Biomarkers; D001823:Body Composition; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology* / Q000209:etiology*; D009929:Organ Size; D018384:Oxidative Stress; D011159:Population Surveillance; D011470:Prostatic Hyperplasia / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D012307:Risk Factors; D013714:Tennessee / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators