title: Changes of urinary bladder contractility in high-fat diet-fed mice: the role of tumor necrosis factor-α.
abstract: OBJECTIVE
  To study the role of tumor necrosis factor-α 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-α antagonist) treatment was given during the last 4 weeks. At the end of the treatment period, serum tumor necrosis factor-α, total cholesterol, triglyceride and blood glucose were measured. Bladder strip contractile responses to 1 μmol/L acetylcholine or 50 mmol/L KCl were studied in an organ bath. Bladder protein kinase Cζ, nuclear factor-κB and intercellular adhesion molecule-1 expressions were analyzed using western blots.
  
  
  RESULTS
  Serum levels of tumor necrosis factor-α 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 Cζ, nuclear nuclear factor-κB and intercellular adhesion molecule-1. Etanercept restored normal bladder contractile responses, as well as protein kinase Cζ nuclear factor-κB and intercellular adhesion molecule-1 expressions.
  
  
  CONCLUSIONS
  A high-fat diet induces bodyweight gain, hyperlipidemia and hyperglycemia in mice. Elevated serum tumor necrosis factor-α level associated with increased protein kinase Cζ phosphorylation, nuclear factor-κB nuclear migration, intercellular adhesion molecule-1 expression and impaired muscle contractility are shown in the high-fat diet-fed mouse bladder. Tumor necrosis factor-α antagonist treatment restores normal bladder contractility, and protein kinase Cζ nuclear factor-κB and intercellular adhesion molecule-1 levels.
authors.affiliation: Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Eric Wen-Chou
authors.initials: EW
authors.lastname: Fan
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.forename: Yat-Ching
authors.initials: YC
authors.lastname: Tong
mesh_terms: D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000150:complications*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D001745:Urinary Bladder Diseases / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D000099221:Protein Kinase C zeta
chemical_list: D000068800:Etanercept; D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1; D016328:NF-kappa B; D011493:Protein Kinase C; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000099221:Protein Kinase C zeta
keywords: bladder dysfunction; high-fat diet; metabolic syndrome; obesity; tumor necrosis factor-α