Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome

Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Yehiely‐Cohen, Ravit; Maneschi, Elena; Gacci, Mauro; Carini, Marco; Adorini, Luciano; Vannelli, Gabriella Barbara; Maggi, Mario

doi:10.1016/j.jsbmb.2012.02.007

Cited by 69 publications

(86 citation statements)

References 47 publications

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“…In particular, we observed severe inflammation, running in parallel with hypoxia and tissue remodelling, both in prostatic and bladder tissue [22,28].…”

Section: Discussionmentioning

confidence: 80%

“…LUTS were measured by the IPSS and categorised as storage and voiding symptoms, immediately before surgery and at 6-12 months postoperatively. The total IPSS score was categorised into 0-7, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]; storage subscore into 0-5, 6-9 and 10-15; voiding subscore into 0-6, 7-13 and 14-20 as mild, moderate and severe, respectively. For all IPSS (total, storage and voiding) the percentage of recovery of urinary symptoms after the operation (total-, storage-and voiding-Δ IPSS) was calculated using the following method: ([Preoperative IPSS -Postoperative IPSS]/Preoperative IPSS), expressed as a percentage: the full recovery of lower urinary tract function was considered as Δ = 100%.…”

Section: Methodsmentioning

confidence: 99%

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Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study

et al. 2015

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Objective To evaluate the impact of components of metabolic syndrome (MetS) on urinary outcomes after surgery for severe lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), as central obesity can be associated with the development of BPE and with the worsening of LUTS. Patients and Methods A multicentre prospective study was conducted including 378 consecutive men surgically treated for large BPE with simple open prostatectomy (OP) or transurethral resection of the prostate (TURP), between January 2012 and October 2013. LUTS were measured by the International Prostate Symptom Score (IPSS), immediately before surgery and at 6–12 months postoperatively. MetS was defined according the USA National Cholesterol Education Program‐Adult Treatment Panel III. Results The improvement of total and storage IPSS postoperatively was related to diastolic blood pressure and waist circumference (WC). A WC of >102 cm was associated with a higher risk of an incomplete recovery of both total IPSS (odds ratio [OR] 0.343, P = 0.001) and storage IPSS (OR 0.208, P < 0.001), as compared with a WC of <102 cm. The main limitations were: (i) population selected from a tertiary centre, (ii) Use exclusively of IPSS questionnaire, and (iii) No inclusion of further data. Conclusions Increased WC is associated with persistent postoperative urinary symptoms after surgical treatment of BPE. Obese men have a higher risk of persistent storage LUTS after TURP or OP.

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“…In particular, we observed severe inflammation, running in parallel with hypoxia and tissue remodelling, both in prostatic and bladder tissue [22,28].…”

Section: Discussionmentioning

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study

et al. 2015

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“…This notion mainly stems from preclinical studies, which have provided a great deal of information about an association between metabolic diseases and LUT alterations. 28,29 Our laboratory has developed, over the last few years, an animal model of MetS by feeding adult male rabbits a high-fat diet for twelve weeks. [28][29][30][31] Interestingly, high-fat diet induced not only the classical features of MetS (overt dyslipidaemia, hypertension, hyperglycemia, insulin resistance and increased visceral adiposity), but also a marked inflammation and stromal derangement in the whole of the LUT, including the prostate 28 and bladder.…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Our laboratory has developed, over the last few years, an animal model of MetS by feeding adult male rabbits a high-fat diet for twelve weeks. [28][29][30][31] Interestingly, high-fat diet induced not only the classical features of MetS (overt dyslipidaemia, hypertension, hyperglycemia, insulin resistance and increased visceral adiposity), but also a marked inflammation and stromal derangement in the whole of the LUT, including the prostate 28 and bladder. 29 From a pathophysiological standpoint, dyslipidemia is the bestrecognized pro-inflammatory factor among all the others MetS features, leading to inflammation and pro-atherogenic remodeling of the vascular wall.…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome and lower urinary tract symptoms: the role of inflammation

Gacci

Vignozzi

Sebastianelli

et al. 2012

Prostate Cancer Prostatic Dis

143

137

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BACKGROUND: Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities. Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens. METHODS: A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker. RESULTS: Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume 460 cm 3 (hazard ratio (HR) ¼ 3.268, Po0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Q max ): 8.6 vs 10.1, P ¼ 0.008 and average flow rate (Q ave ): 4.6 vs 5.3, P ¼ 0.033, respectively), and higher obstructive urinary symptoms score (P ¼ 0.064). A positive correlation among both IS-GD and IPSS Score was also observed (adjusted r ¼ 0.172, P ¼ 0.008 and adjusted r ¼ 0.128, P ¼ 0.050). CONCLUSIONS: MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.

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“…In their experiment, HFD-animals develop hypogonadism and all the MetS features like hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. A recently established rabbit model of HFD-induced MetS showed hypogonadism and the presence of prostate gland alterations, including inflammation, hypoxia and fibrosis [120]. Rabbits fed a cholesterol-rich diet (1% cholesterol) for 8 weeks and 12 weeks share several physiopathological aspects of NAFLD [121].…”

Section: The Rabbit Modelsmentioning

confidence: 99%

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

Karimi¹

2012

Lipoproteins - Role in Health and Diseases

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Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome

Cited by 69 publications

References 47 publications

Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study

Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study

Metabolic syndrome and lower urinary tract symptoms: the role of inflammation

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

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