Adiponectin Signaling Regulates Urinary Bladder Function by Blunting Smooth Muscle Purinergic Contractility

Area of Science:

• Endocrinology
• Urology
• Metabolic Syndrome Research

Background:

• Lower urinary tract symptoms (LUTS) affect over 50% of individuals over 40 and are linked to obesity and metabolic syndrome.
• Adipose tissue releases adipokines, like adiponectin (ADPN), which regulate metabolism and inflammation, but their role in LUTS is unclear.

Purpose of the Study:

• To investigate the role of adiponectin (ADPN) in regulating bladder function and its potential involvement in LUTS associated with metabolic dysfunction.

Main Methods:

• Utilized a global ADPN knockout mouse model (Adpn-/-) to assess bladder function.
• Examined voiding patterns, bladder smooth muscle (BSM) contractility, and molecular pathways.
• Administered ADPN receptor agonist (AdipoRon) and AMPK modulators to evaluate their effects on BSM contraction.

Main Results:

• Adpn-/- mice displayed increased urination frequency, smaller void volumes, and diminished BSM contractility, notably lacking purinergic contraction.
• Molecular analysis revealed significant alterations in metabolic and purinergic signaling pathways in Adpn-/- mice.
• AdipoRon treatment abolished acute BSM contraction, and both AMPK activators and inhibitors also inhibited BSM purinergic contraction.

Conclusions:

• A novel ADPN signaling pathway is crucial for regulating BSM contractility.
• Dysregulation of this ADPN pathway may represent a key mechanism underlying LUTS in obesity and metabolic syndrome.