Impairment of autophagy may represent the molecular mechanism behind the relationship between obesity and inflammation in patients with BPH and LUTS.

ABSTRACT

BACKGROUND: Aim of this study was to evaluate the roles of inflammation and autophagy in obese patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). METHODS: We analyzed 150 surgical specimens from patients underwent transurethral resection of the prostate (TURP) for LUTS/BPH (Median age 70.3±8.1 years, median BMI 25.7±4.0 kg/m2 and median PSA 6.0±5.4 ng/mL). All surgical specimens were investigated for the presence inflammatory infiltrates, according to the standardized classification of chronic prostatitis of the National Institute of Health. The inflammatory score (IS Score) was calculated. High IS score was defined as ≥7. Each sample was stained for anti-LC3B (cell signaling) and for anti-P62/SQSTM1 (MBL) according to manufacturer's suggestions and scored as follow 0 (no dots); 1 (detectable dots in 5-25% of cells); 2 (readily detectable dots in 25-75% of cells); 3 (dots in >75% of cells). High percentage of p62 or LC3B was defined as >25%, whereas low percentage of p62 or LC3B was defined as <25% of cells with dots. RESULTS: Overall 74/150 (49.3%) patients were overweight or obese (BMI >25 kg/m2). Obese patients presented a higher inflammatory score. Obese/overweight patients presented a lower percentage of LC3B (58/74; 78.4%) and higher of p62 (49/74; 66.2%) compared to those of normal weight, which it means a deactivated autophagy (P<0.05). At multivariate analysis LC3B (OR=0.22; CI 0.069-0.70; P=0.01) percentage and BMI (OR=1.118; CI 1.001-1.250; P=0.04) were independent risk factors of prostatic inflammation (IS≥7). CONCLUSIONS: Here we confirm the association between obesity and prostatic inflammatory infiltrates and present the first evidence of autophagy deregulation in obese patients with LUTS/BPH. Further studies should better investigate this relationship and provide new possible therapeutic targets.