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Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet

  • Original Article—Alimentary Tract
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Abstract

Background

Advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) are closely associated with colorectal cancer progression. The association between RAGE and AGE in colon carcinogenesis needs to be clarified.

Methods

Levels of RAGE and AGE were examined in azoxymethane (AOM)-injected Fischer 344 rats fed a control diet (Group C), a 15 % linoleic acid (LA) diet (Group L), a control diet with 10 % glucose drink (Group G), and a 15 % LA diet with 10 % glucose drink (Group L + G). Group L + G showed the most pronounced increase of body weight, blood sugar, and serum insulin.

Results

The rats in Group L + G showed the most pronounced multiplicity of aberrant crypt foci (ACF) and carcinomas with increased mucosal RAGE and AGE. IEC6 rat intestinal epithelial cells treated with AGE showed increased RAGE expression, which was inhibited by treatment with metformin or losartan. In the AOM-injected rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF and carcinomas, in Group L + G rats were suppressed by treatment with metformin or losartan.

Conclusions

These results suggest that AGE–RAGE induced by high-LA and high-glucose diets substantially enhances colon cancer development; thus, suppression of AGE–RAGE could be a potential target for colon cancer chemoprevention.

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Abbreviations

AGE:

Advanced glycation end products

RAGE:

Receptor for advanced glycation end products

CRC:

Colorectal cancer

LA:

Linoleic acid

AOM:

Azoxymethane

ROS:

Reactive oxygen species

PUFA:

Polyunsaturated fatty acid

BSA:

Bovine serum albumin

MMP:

Matrix metalloproteinase

VEGF:

Vascular endothelial growth factor

iNOS:

Inducible nitric oxide synthase

ACF:

Aberrant crypt foci

HMGB:

High mobility group box

NF:

Nuclear factor

ERK:

Extracellular signal-regulated kinase

JNK:

c-Jun N-terminal kinase

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Conflict of interest

We declare that there is no financial support and no relationships which may pose a conflict of interest in the contents of the submitted manuscript. All authors have approved the comments.

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Authors and Affiliations

  1. Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Takasumi Shimomoto, Yi Luo, Hitoshi Ohmori, Yoshitomo Chihara, Kiyomu Fujii, Tomonori Sasahira, Ayumi Denda & Hiroki Kuniyasu

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  1. Takasumi Shimomoto
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Correspondence to Hiroki Kuniyasu.

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Shimomoto, T., Luo, Y., Ohmori, H. et al. Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet. J Gastroenterol 47, 1073–1083 (2012). https://doi.org/10.1007/s00535-012-0572-5

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