Preclinical animal models of lower urinary tract dysfunction associated with metabolic syndrome

Lower urinary tract dysfunction (LUTD) substantially affects quality of life and is increasingly associated with metabolic syndrome (MetS). An intricate relationship exists between MetS components, such as obesity, diabetes, dyslipidaemia and hypertension, and bladder dysfunction. Insights from preclinical models show that MetS-driven autonomic dysfunction, increased intra-abdominal pressure, chronic bladder ischaemia, low-grade inflammation, dysregulated nutrient-sensing pathways and an altered oestrogen-to-testosterone ratio contribute to lower urinary tract symptoms. Diabetic models, such as streptozotocin-induced rodents and polygenic TallyHo mice, show biphasic diabetic LUTD progression, from detrusor hyperactivity to underactivity, driven by hyperglycaemia and neural degeneration. Obesity models, such as leptin-deficient ob/ob mice, undergo prostate and urethral changes exacerbating lower urinary tract symptoms, whereas dyslipidaemia models, such as Apoe^-/- mice, show ischaemia-induced bladder remodelling. Hypertension and early-life stress further worsen LUTD through angiotensin-mediated pathways and visceral adiposity, respectively. Preclinical models provide important insights in this context but face limitations, including non-physiological bladder filling rates and interspecies differences, necessitating advanced approaches such as multi-omics and patient-derived urinoids. These tools could facilitate personalized therapies by elucidating disease mechanisms and enabling longitudinal monitoring but ethical challenges associated with clinical translation persist.