title: Molecular fingerprint of high fat diet induced urinary bladder metabolic dysfunction in a rat model.
abstract: OBJECTIVE
  Diabetic voiding dysfunction has been reported in epidemiological dimension of individuals with diabetes mellitus. Animal models might provide new insights into the molecular mechanisms of this dysfunction to facilitate early diagnosis and to identify new drug targets for therapeutic interventions.
  
  
  METHODS
  Thirty male Sprague-Dawley rats received either chow or high-fat diet for eleven weeks. Proteomic alterations were comparatively monitored in both groups to discover a molecular fingerprinting of the urinary bladder remodelling/dysfunction. Results were validated by ELISA, Western blotting and immunohistology.
  
  
  RESULTS
  In the proteome analysis 383 proteins were identified and canonical pathway analysis revealed a significant up-regulation of acute phase reaction, hypoxia, glycolysis, β-oxidation, and proteins related to mitochondrial dysfunction in high-fat diet rats. In contrast, calcium signalling, cytoskeletal proteins, calpain, 14-3-3η and eNOS signalling were down-regulated in this group. Interestingly, we found increased ubiquitin proteasome activity in the high-fat diet group that might explain the significant down-regulation of eNOS, 14-3-3η and calpain.
  
  
  CONCLUSIONS
  Thus, high-fat diet is sufficient to induce significant remodelling of the urinary bladder and alterations of the molecular fingerprint. Our findings give new insights into obesity related bladder dysfunction and identified proteins that may indicate novel pathophysiological mechanisms and therefore constitute new drug targets.
authors.affiliation: Department of Cardiac Surgery, University of Leipzig, Heart Center Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Oberbach
authors.forename: Nico
authors.initials: N
authors.lastname: Jehmlich
authors.forename: Nadine
authors.initials: N
authors.lastname: Schlichting
authors.forename: Marco
authors.initials: M
authors.lastname: Heinrich
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lehmann
authors.forename: Henry
authors.initials: H
authors.lastname: Wirth
authors.forename: Holger
authors.initials: H
authors.lastname: Till
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Jochen
authors.initials: J
authors.lastname: Neuhaus
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D010641:Phenotype; D020543:Proteome; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D001743:Urinary Bladder / Q000378:metabolism; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000503:physiopathology
chemical_list: D020543:Proteome