Pioneering work from Dr. Yu's lab has shown that the association between obesity and lower urinary tract symptoms may be due to direct signaling between adipose tissue and bladder smooth muscle (BSM). Fat tissue can function as an important regulator of certain other organ functions through the action of released horomones such as adiponectin. Adiponectin (ADPN) is the most abundant adipokine, and exhibits an inverse association with obesity/metabolic syndrome. ADPN plays a crucial role in metabolic homeostasis through its anti-diabetic and anti-inflammatory effects, and mice lacking ADPN develop insulin resistance, metabolic syndrome, and a shortened lifespan. Their data demonstrated that global ADPN-deleted mice exhibited increased voiding frequency, small voids, and reduced bladder smooth muscle (BSM) contractility, with corresponding metabolic and purinergic pathway changes. Furthermore, activation of ADPN receptor (AdpioR) signaling by agonist AdipoRon profoundly inhibited acute BSM contraction. These data indicate that ADPN plays an important role in regulating acute BSM contractility and chronic BSM cell phenotype. This work has important implications for understanding how obesity and type 2 diabetes stimulate bladder disease pathways and offer the hope for new therapeutic approaches to help the millions of people who suffer from overactive bladder and incontinence.