Accelerated Pancreatic Cancer Growth: High Fat Diet Or Obesity?

Abstract

Introduction: Obesity is a well accepted risk factor for development and accelerated growth of pancreatic cancer. We have reported increased pancreatic cancer growth in two discrete murine models of obesity: congenital obesity and obesity induced by high-fat diet (HFD). In the HFD model, not all mice on HFD become obese; nevertheless, pancreatic cancer size correlates directly with body weight. The current study was undertaken to evaluate the hypothesis that obesity, rather than high-fat diet is responsible for accelerated pancreatic cancer growth. Methods: Thirty male C57BL/6J mice were studied. At 5 weeks of age, 20 mice were fed high fat diet (60% fat; HFD) and 10 were fed 10% fat (low fat) diet. At 19 weeks of age, all mice were inoculated in the flank with Pan02 murine pancreatic cancer cells. After 5 weeks of tumor growth, sera and tumors were collected. Apoptosis was determined by apoptag assay. Serum was analyzed by ELISA and colorimetric assay for insulin, glucose, leptin, and adiponectin. Student's t-test, Wilcoxian Rank-Sum, and Pearson's correlation were applied where appropriate. Two way ANOVA was used to determine whether differences were related to diet or weight. P<0.05 was accepted as statistically significant. Results: Two way ANOVA showed that diet did not influence tumor weight (p=0.58); however, tumor weight had a strong positive correlation with body weight (p=0.005). As we have previously described, mice were segregated into overweight (OW - heavier than the mean body weight of HFD mice–35.5g, n=15) and lean (less than 35.5g, n=14). Two thirds of animals in each group had been fed the HFD. Tumors in OW mice were twice as large as those in lean animals (1.23±0.2g vs 0.6±0.1g; p=0.001). Tumors in OW mice had significantly fewer apoptotic cells than those in lean mice (0.8±0.4 vs 2.4±0.5; p<0.05). No changes in serum insulin, glucose, or leptin were observed between groups. Serum adiponectin had a strong negative correlation with tumor size (R=0.45; p<0.05) Conclusions: These data show that: 1) high fat diet did not influence the growth of murine pancreatic cancer; 2) Tumor size correlated positively with body weight; 3) Tumors were significantly larger in overweight compared to lean mice; 4) Tumors in overweight mice had significantly fewer apoptotic cells than those in lean mice; and 5) Serum adiponectin had a significant negative correlation with tumor size. We conclude that obesity, rather than diet influences the accelerated pancreatic cancer growth observed in obesity.