Obesity influence on bladder inflammation and cancer: a cystitis model

Background: Recently, the role of subclinical inflammation in obesity has gained prominence. An association between obesity and chronic inflammation has been observed in several studies that show a relationship between increased morbidity and high Body Mass Index (BMI). This study aims to compare inflammatory pathways in obese (by high-fat diet) and non-obese mice after exposure to an intravesical carcinogen in a cystitis model. Methods: We divided 16 female, 7 week old mice into two groups: 1) CONTROL: standard diet, and 2) OBESE: high fat diet for 8 weeks. Both groups underwent a protocol for N-Nitroso-N-methylurea (MNU) pro-inflammatory bladder instillation. Bladder was analyzed by histopathology and western blotting for proteins of the inflammatory pathway (JNK, NFκB, c-JUN, IKK), and immunohistochemistry (proliferation and apoptosis). Results: While mice eating standard diet showed minimal histologic alteration in 4 of 5 (80%) bladder tissues, those eating a high fat diet showed moderate (60%) and intense (40%) chronic active inflammation with dysplasia foci, increased proliferation, apoptosis and inflammatory pathway activation with increased NFκB, and also IKKβ, JNK, and c-JUN phosphorylation in the urothelium. Conclusion: A high-fat diet causes increased urothelial proliferation, apoptosis, and NFκB expression with cystitis exacerbation and dysplasia. Together, these results suggest that obesity induced by a high-fat diet increases the inflammatory pathway in the bladder with possible pre-malignant alterations.