Obesity-induced diabetes and lower urinary tract fibrosis promote urinary voiding dysfunction in a mouse model

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...

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Published in:	The Prostate Vol. 73; no. 10; pp. 1123 - 1133
Main Authors:	Gharaee-Kermani, Mehrnaz, Rodriguez-Nieves, Jose A., Mehra, Rohit, Vezina, Chad A., Sarma, Aruna V., Macoska, Jill A.
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-07-2013 Wiley Subscription Services, Inc
Subjects:	Animals bladder collagen Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - pathology Diabetes Mellitus, Type 2 - physiopathology diet Diet, Fat-Restricted Diet, High-Fat Dietary Fats Disease Models, Animal fat Fibrosis Glucose Tolerance Test Insulin - blood Lower Urinary Tract Symptoms - etiology Lower Urinary Tract Symptoms - pathology Lower Urinary Tract Symptoms - physiopathology Male Mice Obesity - complications Obesity - pathology Obesity - physiopathology prostate Prostate - pathology Prostate - physiopathology
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Summary:	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. Prostate 73: 1123–1133, 2013. © 2013 Wiley Periodicals, Inc.
Bibliography:	Michigan Institute for Clinical & Health Research (MICHR) NIH Clinical & Translational Science Award (CTSA) - No. UL1RR024986 National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Award - No. P20DK090770 ArticleID:PROS22662 istex:AC8DB4E6A96F91A75AF22B49624249B0452E87FC ark:/67375/WNG-XMKVDX7Z-4 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0270-4137 1097-0045
DOI:	10.1002/pros.22662