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The role of fat diet and physical activity in the molecular alterations of the estrogen pathway in rats' bladders

Grant number: 15/22248-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2016
Effective date (End): January 31, 2017
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Alberto Azoubel Antunes
Grantee:Ana Paula Schreiner
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Obesity and metabolic syndrome (MS) are considered serious threats to public health. Increasing occurrence of these diseases in the world population is simultaneous to the growing incidence of urological complications, highlighting the Lower Urinary Tract Symptoms (LUTS), in which disorders such as overactive bladder occupy a prominent role. Previous comparative studies revealed that the bladder dysfunction associated to MS goes beyond association with prostatic alterations, since similar results were observed in women. Still others have suggested that prevention of MS through behavioral measures, being obesity a major target for intervention, can have a positive effect on symptoms and progression of LUTS. In the search for new mechanisms that explain these changes, recent researches have focused on the influence of estrogens, obtaining positive correlations between increased levels of these hormones (such as changes in the estrogen / testosterone ratio and increasing in 17²-estradiol) and the development of LUTS, like bladder dysfunction. These substances act by interacting with multiple receptors, but the molecular basis for these effects remains unknown. Thus, it is understood the importance of subsequent studies to confirm the role of estrogens in the development of LUTS. Therefore, the project's overall objective is to deepen the knowledge of the bladder morphofunctional alterations resulting from obesity and MS, focusing on the molecular changes of the estrogen pathway and the influence of physical activity.For this purpose, Winstar type mice will be randomized as to the high fat diet and physical activity. The analyzed parameters include histological and morphometric alterations in bladder tissue, with regard to the condition of the detrusor muscle layer, the amount of fibrosis, and the relationship between these two parameters and functional cystometric alterations, which will be assessed through urodynamic study. In the context of the expected molecular changes, the focus will be acting estrogen pathways intranuclear (MAPK and EGFR) and extranuclear (GPR30), as well as the value of CPK and the expression of receptors ER± and Er², through PCR technique. The corresponding serum metabolic parameters such as leptin levels, aromatase, SHBG, glycemia, insulin, estrogen and testosterone (including the relationship between them) will be assessed by ELISA.Statistical analysis will be performed using the SPSS 19.0 for Windows software, comparing quantitative variables among the four groups using ANOVA. To compare values of nominal scale, the chi-square test will be used, with a statistically significant p value less than or equal to 0.05.

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