Lin Wang1,2, Guiting Lin1, Yung-Chin Lee1,3, Amanda B Reed-Maldonado1, Melissa T Sanford1, Guifang Wang1, Huixi Li1,2, Lia Banie1, Zhengcheng Xin2, Tom F Lue1. 1. Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA. 2. Department of Urology, Peking University First Hospital, Peking University, Beijing, China. 3. Department of Urology, Faculty of Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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). MATERIALS AND METHODS: Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Leprfa 186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Leprfa 185; 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. CONCLUSION: 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.
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). MATERIALS AND METHODS: Two study arms were created: a ZL arm including 16-week-old female ZLrats (ZUC-Leprfa 186; n = 12) and a ZF arm including 16-week-old female ZFrats (ZUC-Leprfa 185; 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 ZFrats had insulin resistance, a greater voiding frequency and lower LPP compared with ZLrats (P < 0.05), with more IMCL deposition localized in the urethral striated muscle fibres of the ZFrats (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 ZLrats. CONCLUSION:Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZFrats could be a consistent and reliable animal model in which to study obesity-associated SUI.
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