10.1371/journal.pone.0066636 Andreas Oberbach Andreas Oberbach Nico Jehmlich Nico Jehmlich Nadine Schlichting Nadine Schlichting Marco Heinrich Marco Heinrich Stefanie Lehmann Stefanie Lehmann Henry Wirth Henry Wirth Holger Till Holger Till Jens-Uwe Stolzenburg Jens-Uwe Stolzenburg Uwe Völker Uwe Völker Volker Adams Volker Adams Jochen Neuhaus Jochen Neuhaus Molecular Fingerprint of High Fat Diet Induced Urinary Bladder Metabolic Dysfunction in a Rat Model Public Library of Science 2013 Anatomy and physiology Cell physiology Biochemistry proteins Acute phase proteins Immune system proteins proteome immunochemistry histology Model organisms Animal models rat Molecular cell biology proteomics Protein abundance systems biology Physiological processes Energy metabolism Metabolic disorders nutrition obesity urology Bladder and ureteric disorders fingerprint induced urinary bladder metabolic dysfunction 2013-06-24 02:46:27 Dataset https://plos.figshare.com/articles/dataset/_Molecular_Fingerprint_of_High_Fat_Diet_Induced_Urinary_Bladder_Metabolic_Dysfunction_in_a_Rat_Model_/729812 <div><p>Aims/hypothesis</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions/interpretation</p><p>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.</p></div>