title: High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity.
abstract: 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 Apc(Min/+) 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.
authors.affiliation: Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Daegu, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Daegu, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea.
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Seo
authors.affiliation: School of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, Daegu, Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Sung
keywords: Apc; Colon neoplasms; High-fat diet; Mice; Oxidative stress; Permeability