The interaction of a high-fat diet and regular moderate intensity exercise on intestinal polyp development in Apc Min/+ mice

Abstract

Diet and exercise are two environmental factors that can alter colon cancer risk. The purpose of this study was to determine if regular moderate-intensity treadmill exercise training could attenuate polyp formation in Apc(Min/+) mice fed the Western-style diet. Four-week-old male Apc(Min/+) mice (n = 12 per group) were assigned to AIN-76A Control, AIN-76A Exercise, Western Control, or Western Exercise treatment groups. Mice were weaned to these diets and either subjected to regular moderate-intensity treadmill exercise (18 m/min, 60 min/d, 6 d/wk) or remained sedentary for 6 weeks. Mice fed the Western-style diet consumed approximately 14% more calories and had 42% more epididymal fat compared with mice fed the AIN-76A diet. Exercise had no effect on fat pad mass with either diet treatment. Exercise reduced total intestinal polyp number by 50% and the number of large polyps (>1 mm diameter) by 67% in AIN-76A-fed mice. The Western-style diet increased polyp number by 75% when compared with AIN-76A-fed mice, but exercise did not decrease polyp number or alter polyp size in mice fed the Western-style diet. Markers of systemic inflammation and immune system function were improved with exercise in mice fed the AIN-76A diet. Mice fed the Western-style diet showed more inflammation and immunosuppression, which were not completely ameliorated by exercise. These data suggest that the induction of adiposity, inflammation, and immunosuppression by the Western-style diet may compromise the beneficial effect of moderate-intensity exercise on the intestinal polyp burden in Apc(Min/+) mice.

Figure 1

Total intestinal polyp number, location, and size in 10-week male Apc^Min/+ mice fed an AIN-76A or Western-style diet following 6 weeks of treadmill training. A. Total number of polyps. B. Location of polyps. C. Large polyps. Large polyps were defined as ≥1 mm in diameter. B. Small polyps. Small polyps were defined as <1 mm in diameter. *Denotes significant difference from AIN-76A Control. †Denotes significant difference from AIN-76A Exercise. **Denotes main effect of diet.

Figure 2

β-catenin-positive polyps in 10-week male Apc^Min/+ mice fed an AIN-76A or Western-style diet following 6 weeks of treadmill training. A. Example of β-catenin-positive polyp. B. Number of β-catenin-positive polyps. *Denotes significant difference from AIN-76A Control. †Denotes significant difference from AIN-76A Exercise.

Figure 3

Relationship between epididymal fat pad mass, circulating leptin, and polyp number in 10-week male Apc^Min/+ mice fed an AIN-76A or Western-style diet following 6 weeks of treadmill training. A. Epididymal fat pad mass. B. Circulating leptin. C. Correlation between polyp number and epididymal fat pad mass (r=-0.030; P=0.841). D. Correlation between polyp number and circulating leptin (r=0.114; P=0.580). **Denotes main effect of diet.

Figure 4

Inflammatory and immune state in 10-week male Apc^Min/+ mice fed an AIN-76A or Western-style diet following 6 weeks of treadmill training. A. Plasma haptoglobin. B. Spleen mass. C. Total white blood cell count. D. Monocytes and Granulocytes. *Denotes significant difference from AIN-76A Control. †Denotes significant difference from AIN-76A Exercise. ‡Denotes significant difference from Western Control. **Denotes main effect of diet.