Adiponectin signaling regulates urinary bladder function by blunting smooth muscle purinergic contractility

Area of Science:

• Urology
• Metabolic Syndrome Research
• Molecular Biology

Background:

• Lower urinary tract symptoms (LUTS) affect over 50% of adults over 40 and are strongly linked to obesity and metabolic syndrome.
• Adipokines, released by adipose tissue, regulate metabolism and inflammation; adiponectin (ADPN) is a key adipokine with insulin-sensitizing and anti-inflammatory properties.
• The role of ADPN in LUTS associated with metabolic syndrome is currently unknown.

Purpose of the Study:

• To investigate the potential role of adiponectin (ADPN) in lower urinary tract symptoms (LUTS) associated with obesity and metabolic syndrome.
• To examine the function of ADPN signaling in bladder smooth muscle (BSM) contractility using a global ADPN-knockout mouse model.

Main Methods:

• Utilized global ADPN-knockout (Adpn-/-) mice to assess bladder function and contractility.
• Analyzed metabolic and purinergic pathways in Adpn-/- mice.
• Investigated the effects of the ADPN receptor agonist AdipoRon and AMPK modulators on BSM contractility.

Main Results:

• Adpn-/- mice displayed increased urinary frequency, smaller void volumes, and significantly reduced bladder smooth muscle (BSM) contractility, notably lacking purinergic contraction.
• Molecular analysis revealed significant alterations in metabolic and purinergic pathways in Adpn-/- mice.
• The ADPN receptor agonist AdipoRon, as well as both AMPK activators and inhibitors, abolished acute BSM purinergic contraction.

Conclusions:

• A novel ADPN signaling pathway significantly contributes to the regulation of BSM contractility.
• Dysregulation of this ADPN signaling pathway may represent a key mechanism underlying LUTS in obesity and metabolic syndrome.