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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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Background: 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. Methods: 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. Results: 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). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis. (J Cancer Prev 2016;21:95-103)
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참고문헌 (42)
참고문헌 신청
World Health Organization / Cancer Incidence and Mortality Worldwide: IARC
Tárraga López PJ / 2014 / Primary and secondary prevention of colorectal cancer / Clin Med Insights Gastroenterol 7:33~46
Ames BN / 2001 / DNA damage from micronutrient deficiencies is likely to be a major cause of cancer / Mutat Res 475:7~20
Ju J / 2003 / Effects of green tea and high-fat diet on arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane-induced colon carcinogenesis mouse model / Nutr Cancer 46:172~178
Laugerette F / 2011 / Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation / Biochimie 93:39~45
Tárraga López PJ / 2014 / Primary and secondary prevention of colorectal cancer / Clin Med Insights Gastroenterol 7:33~46
Ames BN / 2001 / DNA damage from micronutrient deficiencies is likely to be a major cause of cancer / Mutat Res 475:7~20
Ju J / 2003 / Effects of green tea and high-fat diet on arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane-induced colon carcinogenesis mouse model / Nutr Cancer 46:172~178
Laugerette F / 2011 / Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation / Biochimie 93:39~45
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