Effect of a high-fat diet in development of colonic adenoma in an animal model.

AIM

To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.

METHODS

Wistar rats were divided into two groups that were fed either a high-fat diet (HFD) or a normal-fat diet (ND), and 1,2-dimethylhydrazine was administered at a dose of 40 mg/kg for 10 wk. The body weight/liver weight/epididymal fat weight were recorded after rats were sacrificed, and the formation of colonic adenoma was also observed. The levels of insulin, leptin, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1 and triglycerides were determined by enzyme-linked immunosorbent assay in order to compare the altered levels of biochemical indices and inflammatory cytokines in the serum between rats fed an ND and HFD. Cell proliferation activity (Ki-67) was determined by immunohistochemical analysis. Western blot and immunofluorescence staining were used to examine the expression of proliferating cell nuclear antigen (PCNA), cyclooxygenase (COX)-2, cyclin D1, β-catenin and nuclear factor (NF)-κB proteins in the adenoma and comparative control tissues.

RESULTS

The number of colonic adenomas and the colonic epithelial Ki-67 were significantly higher in the HFD group than in the ND group. The HFD group also had increased body weight, liver weight and epididymal fat weight, which were associated with increased levels of serum insulin, leptin, TNF-α, IGF-1 and triglycerides. HFD induced upregulation of PCNA, COX-2, cyclin D1, β-catenin and NF-κB proteins, as revealed by Western blot and immunofluorescence staining.

CONCLUSION

HFD promotes the formation of colonic adenoma through inflammation, metabolic abnormalities, and increases cell cycle progression.