J Cancer Prev.  2016 Jun;21(2):95-103. 10.15430/JCP.2016.21.2.95.

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

• Park MY
• Kim MY
• Seo YR
• Kim JS
• Sung MK

• KMID: 2353809
• DOI: http://doi.org/10.15430/JCP.2016.21.2.95

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 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.

Keyword

Apc; Mice; Colon neoplasms; High-fat diet; Permeability; Oxidative stress

MeSH Terms

Animals
Biomarkers
Carcinogenesis*
Cell Membrane*
Claudin-1
Colon
Colonic Neoplasms
Connexins
Diet
Diet, High-Fat*
Endotoxemia
Fluorescein
Inflammation
Interleukin-6
Intestinal Mucosa
Membranes
Mice
Occludin
Oxidative Stress
Permeability
Peroxidase
RNA, Messenger
Toll-Like Receptor 4
Biomarkers
Claudin-1
Connexins
Fluorescein
Interleukin-6
Occludin
Peroxidase
RNA, Messenger
Toll-Like Receptor 4