Mouse Model Finds Diet High in Fat and Calories May Accelerate Development of Pancreatic Cancer
Results showed this type of diet “greatly enhances pancreatic inflammation and strongly accelerates pancreatic cancer development in the conditional KrasG12D mouse model,” reported Guido Eibl, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, and a researcher at UCLA's Jonsson Comprehensive Cancer Center.
The investigators randomly allocated offspring of Pdx-1-Cre and LSL-KrasG12D mice to either a diet high in fats (corn oil) and calories (~4,535 kcal/kg; 40% of calories from fats) or a control diet (~3,725 kcal/kg; 12% of calories from fats) for 3 months.
Mice fed the high fat and calories diet gained more weight vs controls (16.9±2.1g vs 7.1±3.1g; P<0.05); in fact, 90% became obese. These mice also developed hyperinsulinemia (501±311pM vs 223±123pM; P=0.047), hyperglycemia (305±58 mg/dl vs 235±71 mg/dl; P=0.034), hyperleptinemia (1375±276pM vs. 515±243pM; P<0.001), and elevated levels of IGF-1 (8.4±6.5ng/ml vs. 3.1±1.2ng/ml; P=0.048).
The pancreas of animals fed the high fat and calories diet “showed robust signs of inflammation with increased numbers of F4/80-positive macrophages, strong COX-2 expression, and increased desmoplastic reaction,” Dr. Eibl noted; number of advanced murine PanIN lesions was also significantly increased (P<0.05). No differences were observed between female/male mice with respect to weight gain, metabolic disturbances, and PanIN lesions.
“This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity,” Dr. Eibl concluded, including defining the role inflammation produced by obesity plays in development of cancer and if agents such as anti-diabetes drugs or fish oil can halt this disease process.