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Journal of Cancer Prevention

Original Article

Journal of Cancer Prevention 2016; 21(2): 95-103

Published online June 30, 2016

© Korean Society of Cancer Prevention

High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity

Mi-Young Park1,*, Min Young Kim2,*, Young Rok Seo3, Jong-Sang Kim4, and Mi-Kyung Sung2

1Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Daegu, Korea, 2Department of Food and Nutrition, Sookmyung Women’s University, Daegu, Korea, 3Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea, 4School of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, Korea

Correspondence to :
Mi-Kyung Sung, Department of Food and Nutrition, Sookmyung Women’s University, 100 Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Korea, Tel: +82-2-710-9395, Fax: +82-2-710-9453, E-mail:, ORCID: Mi-Kyung Sung,

Received: June 6, 2016; Revised: June 16, 2016; Accepted: June 16, 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.



Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in ApcMin/+ mice.


Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression.


HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2′-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05).


HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

Keywords: Apc, Mice, Colon neoplasms, High-fat diet, Permeability, Oxidative stress

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