Changes of urinary bladder contractility in high-fat diet-fed mice: The role of tumor necrosis factor-α

Objectives: To study the role of tumor necrosis factor-a in bladder dysfunction associated with obesity. Methods: Male 8-week-old C57BL/6J mice were divided into three groups: (i) control mice; (ii) vehicle-treated high-fat diet-fed mice; and (iii) etanercept-treated high-fat diet-fed mice. High-fat diet feeding lasted for 12 weeks, vehicle or etanercept (0.8 mg/kg/day, a tumor necrosis factor-alpha antagonist) treatment was given during the last 4 weeks. At the end of the treatment period, serum tumor necrosis factor-alpha, total cholesterol, triglyceride and blood glucose were measured. Bladder strip contractile responses to 1 mu mol/L acetylcholine or 50 mmol/L KCl were studied in an organ bath. Bladder protein kinase C zeta, nuclear factor-kappa B and intercellular adhesion molecule-1 expressions were analyzed using western blots. Results: Serum levels of tumor necrosis factor-a total cholesterol, triglyceride and glucose were significantly elevated in high-fat diet-fed mice; and the levels were not ameliorated by etanercept treatment. High-fat diet-fed mouse bladder showed reduced contractile responses to acetylcholine and KCl stimulation accompanied by high expression levels of phospho-protein kinase C zeta, nuclear nuclear factor-kappa B and intercellular adhesion molecule-1. Etanercept restored normal bladder contractile responses, as well as protein kinase C zeta nuclear factor-kappa B and intercellular adhesion molecule-1 expressions. Conclusions: A high-fat diet induces bodyweight gain, hyperlipidemia and hyperglycemia in mice. Elevated serum tumor necrosis factor-alpha level associated with increased protein kinase C zeta phosphorylation, nuclear factor-kappa B nuclear migration, intercellular adhesion molecule-1 expression and impaired muscle contractility are shown in the high-fat diet-fed mouse bladder. Tumor necrosis factor-alpha antagonist treatment restores normal bladder contractility, and protein kinase C zeta nuclear factor-kappa B and intercellular adhesion molecule-1 levels.