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. Prostate.

Is Periurethral Calcification Associated With Urinary Flow Rate and Symptom Severity in Men With Lower Urinary Tract Symptoms-Benign Prostatic Hyperplasia? A Retrospective Review

“…22,[24][25][26][27] Prostatitis, aging, and metabolic diseases such as type 2 diabetes mellitus induce inflammatory changes, which can associate with the development of prostatic fibrosis. 1,5,[14][15][16]19,28 Similarly, in our study prostatic calcification significantly associated with aging ( Table 2). This relationship was also proven in previous studies.…”

“…Recently, prostatic fibrosis, especially periurethral fibrosis, has been suggested as a novel cause of LUTS in men. 1,5,6,8 Since 2012, the periurethral area has been focused on as a key region determining LUTS severity. Ma et al 6 analyzed periurethral tissues obtained from radical prostatectomies and demonstrated that periurethral tissue from men with LUTS was significantly stiffer with higher collagen content and lower glandularity compared with men without LUTS.…”

Laparoscopic sleeve gastrectomy effects on overactive bladder symptoms

“…In an animal model, insulin resistance contributes to detrusor overactivity, which is a possible cause of OAB symptoms [22]. Other investigations showed that obesity and concurrent type 2 diabetes mellitus lower urinary tract fibrosis and are inextricably and biologically linked to urinary voiding dysfunction [23]. However, the effect of irritation on obesity can be postulated based on the assumption that fat in the pelvis reduces bladder expansion and thus increases urinary frequency and determines low mean urinary volumes for micturition, as showed by voiding diaries in our study.…”

Androgen Deficiency and Progression of Benign Prostatic Hyperplasia in Patients With Metabolic Syndrome: Is There Any Controversy? (A Literature Review)

“…Аналогич-ные данные об усилении фиброза периуретральных отделов ПЖ были получены M. Gharaee-Kermani и соавт. [69] в опытах на мышах, содержащихся на ди-ете, обогащенной жирами, у которых развились ожи-рение и диабет.…”