Fat depot-specific accumulation of benzo(a)pyrene metabolites in rats fed with western diet and its implications for colon cancer.

Obesity is one of the factors that potentiate the development of colorectal cancer (CRC). Our previous studies using a rat model, the Polyposis In the Rat Colon (PIRC) kindred type revealed that compared to regular diet (RD), the Western diet (WD) accelerated the progression of colon tumors caused by benzo(a)pyrene [B(a)P], an environmental toxicant. The objective of this study was to investigate the relationship between B(a)P dose, diet type, and accumulation of B(a)P in different adipose depots and its impact on CRC development. Groups of PIRC rats were fed with AIN-76A standard diet (RD) or Western diet (WD) and received 25, 50, or 100 µg B(a)P/kg body weight via oral gavage for 60 days. After exposure, rats were euthanized; colons were removed, polyp numbers were counted, and adipose tissues from the B(a)P-treated rats were collected for subsequent analysis. The white adipose tissue (WAT) included visceral-, mesenteric-, subcutaneous-, epididymal-, retroperitoneal-, and inguinal fats while the brown adipose tissue (BAT) included mediastinal-, cervical-, interscapular-, and perirenal fats. The plasma and tissue samples were analyzed by reverse phase-HPLC for B(a)P metabolites. The WAT showed significantly greater concentrations of B(a)P metabolites (two- to four-fold increase) compared to BAT in a B(a)P dose-dependent manner. The colon polyp numbers showed a strong correlation with mesenteric- and visceral fat tissues. Our findings indicate that B(a)P accumulated in the adipose tissue will have a greater likelihood of fueling colon tumor growth in long-term exposures.