Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice

Pharmacol Rep. 2020 Feb;72(1):179-187. doi: 10.1007/s43440-019-00010-3. Epub 2020 Jan 8.


Background: Benign prostatic hyperplasia (BPH) is associated with obesity and prostatic inflammation. The present study investigated the participation of toll-like receptor 9 (TLR9) in obesity-induced BPH, focusing on metabolic impairments, damage-associated molecular patterns (DAMP) levels and prostatic oxidative stress generation.

Methods: C57BL/6 (WT) and TLR9 mutant male mice were fed with regular or high-fat diet for 12 weeks. Metabolic profile, functional protocols, reactive-oxygen species (ROS) generation, prostatic histological analysis and DAMP levels were analyzed. Western blotting for prostatic TLR9 signaling pathway was also performed.

Results: BPH in WT obese animals was characterized by increased prostate weight, smooth muscle hypercontractility and prostatic epithelial hyperplasia. Higher epididymal fat weight and prostatic ROS generation along with increased fasting glucose, triglyceride and circulating DAMP levels were also observed in WT obese group. Conversely, TLR9 mutant obese animals exhibited lower epididymal fat weight, fasting glucose and triglyceride levels associated with reduced prostate hypercontractility, prostatic ROS and circulating DAMP levels. However, TLR9 mutant obese mice were not protected from obesity-associated prostatic overgrowth and epithelial hyperplasia. Interestingly, TLR9 mutant lean mice exhibited augmented fasting glucose and prostatic ROS levels compared with WT lean mice. Despite increased prostatic expression of TLR9 in WT obese mice, no differences were seen in MyD88 expression between groups.

Conclusion: Improved obesity-induced BPH-related prostatic smooth muscle hypercontractility in TLR9 obese mice may be associated with amelioration in the metabolic profile, ROS and DAMP generation. Therefore, TLR9 could be a valuable target to improve obesity-associated metabolic disorders and prostate smooth muscle hypercontractility in BPH.

Keywords: HMGB1; High-fat diet; Innate immune system; Prostatic smooth muscle; Reactive-oxygen species.

MeSH terms

  • Alarmins / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Contraction / physiology
  • Muscle, Smooth / metabolism
  • Obesity / complications*
  • Oxidative Stress / physiology*
  • Prostatic Hyperplasia / etiology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / physiopathology*
  • Reactive Oxygen Species / metabolism
  • Toll-Like Receptor 9 / genetics*


  • Alarmins
  • Reactive Oxygen Species
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9