Obesity, But Not High-Fat Diet, Promotes Murine Pancreatic Cancer Growth

Background: Obesity accelerates pancreatic cancer growth; the mechanisms underlying this association are poorly understood. This study evaluated the hypothesis that obesity, rather than high-fat diet, is responsible for accelerated pancreatic cancer growth. Methods: Male C57BL/6J mice were studied after 19 weeks of high-fat (60 % fat; n = 20) or low-fat (10 % fat; n = 10) diet and 5 weeks of Pan02 murine pancreatic cancer growth (flank). Results: By two-way ANOVA, diet did not (p = 0. 58), but body weight, significantly influenced tumor weight (p = 0. 01). Tumor weight correlated positively with body weight (R² = 0. 562; p < 0. 001). Tumors in overweight mice were twice as large as those growing in lean mice (1. 2 ± 0. 2 g vs. 0. 6 ± . 01 g, p < 0. 01), had significantly fewer apoptotic cells than those in lean mice (0. 8 ± 0. 4 vs 2. 4 ± 0. 5; p < 0. 05), and greater adipocyte volume (3. 7 vs. 2. 2 %, p < 0. 05). Apoptosis (R² = 0. 472; p = 0. 008) and serum adiponectin correlated negatively with tumor weight (R = 0. 45; p < 0. 05). Conclusions: These data suggest that body weight, and not high-fat diet, is responsible for accelerated murine pancreatic cancer growth observed in this model of diet-induced obesity. Decreased tumor apoptosis appears to play an important mechanistic role in this process. The concept that decreased apoptosis is potentiated by hypoadiponectinemia (seen in obesity) deserves further investigation.