title: Obesity-induced diabetes and lower urinary tract fibrosis promote urinary voiding dysfunction in a mouse model.
abstract: BACKGROUND
  Progressive aging- and inflammation-associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM).
  
  
  METHODS
  To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis.
  
  
  RESULTS
  The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet-induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis.
  
  
  CONCLUSIONS
  Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked.
authors.affiliation: The Department of Urology, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Gharaee-Kermani
authors.forename: Jose A
authors.initials: JA
authors.lastname: Rodriguez-Nieves
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Chad A
authors.initials: CA
authors.lastname: Vezina
authors.forename: Aruna V
authors.initials: AV
authors.lastname: Sarma
authors.forename: Jill A
authors.initials: JA
authors.lastname: Macoska
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004041:Dietary Fats; D004195:Disease Models, Animal; D005355:Fibrosis; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D059411:Lower Urinary Tract Symptoms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D011467:Prostate / Q000473:pathology / Q000503:physiopathology
chemical_list: D004041:Dietary Fats; D007328:Insulin