title: Transgenic animal model for studying the mechanism of obesity-associated stress urinary incontinence.
abstract: OBJECTIVE
  To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity-associated stress urinary incontinence (SUI).
  
  
  METHODS
  Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Leprfa186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Leprfa185; n = 12). I.p. insulin tolerance testing was carried out before functional study. Metabolic cages, conscious cystometry and leak point pressure (LPP) assessments were conducted. Urethral tissues were harvested for immunofluorescence staining to check intramyocellular lipid (IMCL) and sphincter muscle (smooth muscle and striated muscle) composition.
  
  
  RESULTS
  The ZF rats had insulin resistance, a greater voiding frequency and lower LPP compared with ZL rats (P < 0.05), with more IMCL deposition localized in the urethral striated muscle fibres of the ZF rats (P < 0.05). The thickness of the striated muscle layer and the ratio of striated muscle to smooth muscle were lower in ZF than in ZL rats.
  
  
  CONCLUSIONS
  Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZF rats could be a consistent and reliable animal model in which to study obesity-associated SUI.
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.|Department of Urology, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.|Department of Urology, Faculty of Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yung-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Reed-Maldonado
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Melissa T
authors.initials: MT
authors.lastname: Sanford
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Guifang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.|Department of Urology, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Huixi
authors.initials: H
authors.lastname: Li
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Banie
authors.affiliation: Department of Urology, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Zhengcheng
authors.initials: Z
authors.lastname: Xin
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D005260:Female; D009765:Obesity / Q000150:complications*; D051381:Rats; D011924:Rats, Zucker; D014521:Urethra / Q000503:physiopathology*; D014550:Urinary Incontinence, Stress / Q000209:etiology*
keywords: Zucker fatty rats; intramyocellular lipid; obesity; stress urinary incontinence; urethral sphincter