Periprostatic fat gene expression in male mouse diet induced obesity and calorie restriction study

Obesity is associated with an increased incidence of high grade prostate cancer (PC) and worse prognosis for PC patients. Recently, we showed in men that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures, was associated with high grade PC. Possibly, interventions that suppress periprostatic WAT inflammation will improve outcomes for men with PC. We found that supplemental 17β-estradiol (E2) could decrease periprostatic WAT inflammation in obese male mice in association with reduction in weight and calorie consumption. Here, we tested the hypothesis that calorie restriction alone would have similar effects on periprostatic WAT inflammation in obese male mice. To test this hypothesis, male mice were fed high fat diet to induce obesity and then switched to a 30% caloric restriction diet for an addition 7 weeks until sacrifice. LFD fed mice and mice fed HFD ad libitum serve as controls. Male C57BL/6J mice were obtained from The Jackson Laboratory and fed low fat diet (LFD, 10 kcal% fat, 12450Bi; Research Diets) or high fat diet (HFD, 60 kcal% fat, D12492i) beginning at 6 weeks of age. The mice were continued on these diets for a total of 12 weeks. After 12 weeks of feeding, the HFD fed mice were divided into two groups. One group was fed ad libitum for an additional 7 weeks until sacrifice while the other group was switched to a 30% CR feeding regimen for 7 weeks until sacrifice. Each day for 7 weeks the CR group received 70% of the amount consumed by the HFD group that was fed ad libitum. The LFD group was fed ad libitum for an additional 7 weeks until sacrifice. All mice were sacrificed at 25 weeks of age and periprostatic fat was harvested and snap frozen. Total RNA was isolated and analyzed from 6 LFD, 6 HFD ad libitum, and 5 HFD calorie restricted mice and analyzed by microarray.