Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice.
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
Reactive Oxygen Species
/ metabolism
Toll-Like Receptor 9
/ genetics
HMGB1
High-fat diet
Innate immune system
Prostatic smooth muscle
Reactive-oxygen species
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
04
04
2019
accepted:
10
09
2019
revised:
27
08
2019
entrez:
5
2
2020
pubmed:
6
2
2020
medline:
30
10
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32016843
doi: 10.1007/s43440-019-00010-3
pii: 10.1007/s43440-019-00010-3
pmc: PMC7006691
mid: NIHMS1548621
doi:
Substances chimiques
Alarmins
0
Reactive Oxygen Species
0
Tlr9 protein, mouse
0
Toll-Like Receptor 9
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
179-187Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL134604
Pays : United States
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