Effects of diet-induced obesity on colitis-associated colon tumor formation in A/J mice

Abstract

Objective: Studies have indicated that obesity is associated with a higher risk of colorectal cancer. This study was performed to determine the effect of diet-induced obesity on the formation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumors and to identify adiposity-related mechanisms. Methods: Male A/J mice were placed on either a high-fat diet (HFD; 45% of total calories from fat) or a normal diet (ND; 15% of calories from fat) for 12 weeks. To induce colon tumors, AOM was administered at a dose of 10 mg/kg body weight, followed by two cycles of DSS supply. Results: Study results indicated that the HFD group had twofold higher numbers of colonic tumors, as compared with the ND group. The HFD group also had significantly increased body weight and epididymal fat weight, which were associated with increases of serum insulin, insulin-like growth factor-1, leptin, epididymal fat pad leptin mRNA and colonic leptin receptor (Ob-R) mRNA. Animals on HFD showed higher expressions of Ob-R, insulin receptor, phosphorylated Akt, phosphorylated extracellular signal-regulated kinases, Bcl-xL and Cyclin D1 proteins in the colon. Conclusion:The results suggest that HFD-induced obesity facilitates colon tumor formation, possibly by regulating downstream targets of circulating adiposity-related factors via receptor-mediated signaling of the phosphatidylinositol 3-kinase/Akt pathway.

High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer

“…A study performed by Park et al found that HFD (45% kcal from fat)-induced obesity in male A/J mice facilitated tumor development (34). Contrary to this and consistent with our findings, Boddicker et al showed that a high-fat lard-based diet (60% kcal from fat) significantly decreased total colonic lesions compared with a LFD in male C57BL/6 mice (5).…”

Carnosic acid suppresses colon tumor formation in association with antiadipogenic activity

“…Excess accumulation of adipose tissue results in higher circulating concentrations of insulin, leptin, free fatty acids, and inflammatory cytokines that stimulate cancer cell mitogenesis, angiogenesis, and migration through receptor‐mediated intracellular signaling . In our previous study, elevated colonic expressions of IR and Ob‐R suggested the direct involvement of insulin and leptin in the development of colon tumor formation . Therefore, a strategy to prevent colorectal carcinogenesis might be to avoid excess amounts of circulating growth signaling molecules associated with adipose tissue.…”

NAG-1/GDF15 Transgenic Mouse Has Less White Adipose Tissue and a Reduced Inflammatory Response

“…Leptin is the critical regulator of intestinal inflammation [26] and a number of studies demonstrate that increases or decreases in the serum levels of leptin can, respectively, increase or decrease the AOM-induced and APC min⁡ models of intestinal tumorigenesis [27, 28]. Based on the literature, we propose that the lower white adipose tissue and lower circulating leptin levels may be responsible, in part, for the resistance to intestinal polyps formation observed in the two mouse models of intestinal cancer we previously tested.…”