Metabolic profile alterations in juvenile rats with bladder overactivity induced by short-term high-fructose intake.

Background: Overactive bladder syndrome (OAB) is a common condition that affects both adults and children, often causing significant discomfort and negatively impacting quality of life. This study aimed to preliminarily evaluate whether fructose exposure induces OAB-like symptoms in juvenile rats and to explore potential metabolic mechanisms involved. Methods: Three-week-old female Sprague-Dawley rats were randomly assigned to two groups: a model group fed a 60% fructose diet for one week, and a control group fed a standard diet. Body weight, blood biochemical parameters, urination behavior, and urodynamic function were assessed. Bladder tissue was analyzed using hematoxylin and eosin staining, immunohistochemistry, and immunofluorescence. Molecular and metabolic changes were evaluated via Western blot and metabolomic analysis. Results: Short-term high fructose intake led to significant metabolic and functional changes in juvenile rats. The model group showed reduced body weight and altered lipid metabolism, while glucose and insulin levels remained largely unchanged. Urodynamic assessments revealed increased non-voiding contractions, shortened intervals between contractions, and impaired bladder storage function. Open field tests indicated increased urinary frequency and open field test results. Histological analysis demonstrated disorganized bladder smooth muscle structure and elevated oxidative stress. Metabolomic profiling revealed marked alterations in energy metabolism, including enhanced glycolysis, pentose phosphate pathway activation, and accumulation of ATP and lactate. Western blot analysis confirmed activation of the CaMKK2/AMPK signaling pathway in bladder tissue. Conclusions: Short-term high-fructose intake induces OAB-like symptoms in juvenile rats, accompanied by fructose toxicity, oxidative stress, calcium ion accumulation, and activation of the CaMKK2/AMPK signaling pathway. These findings highlight a potential link between fructose metabolism and bladder dysfunction, offering new insights for exploring metabolic or antioxidant-based therapeutic strategies in pediatric OAB.