Enhancement of Carcinogenesis and Fatty Infiltration in the Pancreas in N-Nitrosobis(2-Oxopropyl)Amine-Treated Hamsters by High-Fat Diet
ABSTRACT Objectives: Obesity is associated with increased pancreatic cancer risk, although the mechanisms have yet to be detailed. This study aimed to elucidate promotion of pancreatic cancer by obesity and hyperlipidemia.
Methods: Six-week-old female Syrian golden hamsters were treated with N-nitrosobis(2-oxopropyl)amine (BOP) and after 1 week were fed a high-fat diet (HFD) or standard diet (STD) for 6 or 17 weeks.
Results: Body weight and serum levels of lipids and leptin were significantly higher in the HFD than the STD group at 14 weeks of age. Pancreatic ductal adenocarcinomas developed only in the BOP + HFD group, with an incidence of 67% (P < 0.01) at 14 weeks of age. In addition, the multiplicity was 2-fold greater in the BOP + HFD group than in the BOP + STD group (P < 0.05) at 25 weeks of age. Pancreatic fatty infiltration was increased by BOP treatment and further enhanced by the HFD, correlating with progression of BOP-induced pancreatic ductal adenocarcinoma and up-regulated expression of adipocytokines and cell proliferation-related genes in the pancreas.
Conclusions: High-fat diet is shown to increase serum lipid levels and enhance fatty infiltration in the pancreas with abnormal adipocytokine production, which may accelerate and enhance pancreatic cancer.