Login to Access Video or Poster Abstract: MP17-15
Sources of Funding: 1R01 DK103483-01

Introduction

Benign prostatic hyperplasia (BPH) is a major public health problem with high morbidity and associated cost. BPH arises in the context well recognized comorbidities including metabolic syndrome (MetS), obesity and diabetes. Animal models do not reflect all aspects of the human disease. Recently, an animal model, leptin-deficient obese ObOb mice has been reported that mimics the features of MetS and prostatic hyperplasia. However, details of the linkage between MetS/obesity and prostatic hyperplasia remain unknown in this model. To assess the relationship between MetS/obesity and prostatic hyperplasia in ObOb mice, we evaluated the morphological phenotype of control and leptin-treated ObOb mice prostate.

Methods

We started with 10-week-old male ObOb and strain-matched control mice. Three groups were examined: lean C57/Bl/6J (strain-matched control), non-treated ObOb, and leptin-treated ObOb mice. Leptin was delivered using a subcutaneous Alzet micro-osmotic pump. Leptin was delivered 5 μg/day for the initial 12 weeks of the study, and at 10 μg/day for the final 12 weeks. The liver, pancreas, spleen, skin, femoral muscle, subcutaneous fat, visceral fat, periprostatic fat, brown fat, and urogenital organs were harvested for analysis.

Results

In ObOb mice, total body weight and liver weight were reduced 25%-35% by leptin treatment. Leptin supplementation dramatically reduced body weight during the first month, but weight then increased slowly. Non-fasting serum blood glucose levels were normal range (≤ 250mg/dl) in all ObOb mice, but a glucose tolerance test revealed significantly longer recoveries in non-treated vs. leptin-treated ObOb mice. Compared to non-treated ObOb mice, liver weight of leptin-treated ObOb mice is significant lighter but still heavier than lean C57/Bl/6J mice. Anterior, ventral, and dorsolateral prostate glands in non-treated ObOb mice exhibited epithelial hyperplasia compared to lean C57/Bl/6J mice. In the leptin-treated mice, the number of hyperplastic prostate glands in each lobe was significant lower than in non-treated ObOb mice.

Conclusions

Our results demonstrated that long-term leptin treatment results in a reduction in prostatic epithelial hyperplasia in the ObOb mouse model. Full characterization of this animal model may elucidate molecular mechanisms linking MetS/obesity and prostatic hyperplasia.

Funding

1R01 DK103483-01