Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2014; 20(25): 8119-8129
Published online Jul 7, 2014. doi: 10.3748/wjg.v20.i25.8119
Effect of a high-fat diet in development of colonic adenoma in an animal model
Qing-Chao Zhu, Ren-Yuan Gao, Wen Wu, Bo-Min Guo, Jia-Yuan Peng, Huan-Long Qin
Qing-Chao Zhu, Ren-Yuan Gao, Wen Wu, Bo-Min Guo, Jia-Yuan Peng, Huan-Long Qin, Department of Surgery, the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China
Author contributions: Zhu QC, Gao RY and Wu W conducted the experiments; Guo BM and Peng JY analyzed the data; Zhu QC wrote the manuscript and Qin HL revised the manuscript; all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81230057
Correspondence to: Huan-Long Qin, MD, PhD, Department of Surgery, the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China. huanlongqin@yahoo.com
Telephone: +86-21-64361349 Fax: +86-21-64361349
Received: December 7, 2013
Revised: March 10, 2014
Accepted: April 5, 2014
Published online: July 7, 2014
Processing time: 208 Days and 2.5 Hours
Abstract

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.

Keywords: High-fat diet; Colonic adenomas; Inflammation; Adipokines

Core tip: This study was undertaken to explore the effect of a high-fat diet on the incidence of colonic adenoma induced by intraperitoneal injection of 1,2-dimethylhydrazine in Wistar rats. We demonstrated that a high-fat diet (HFD) increased the proliferative activity of colonic epithelial cells, and we conclude that HFD-mediated tumor growth could be associated with inflammation and increased cell cycle progression. This study might be conducive to understanding the nature of the relationship between high fat intake and the increased risk of colorectal carcinoma.