Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer

Ildiko Erdelyi, Natasha Levenkova, Elaine Lin, John T. Pinto, Martin Lipkin, Fred W. Quimby, Peter R. Holt

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.

Original languageEnglish (US)
Pages (from-to)2072-2078
Number of pages7
JournalJournal of Nutrition
Volume139
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

Colonic Neoplasms
Colon
Oxidative Stress
Diet
Transcriptome
Colorectal Neoplasms
Mucous Membrane
Macrophages
Aryl Hydrocarbon Receptors
High Fat Diet
Xenobiotics
Lipid Metabolism
Vitamin D
Oxidation-Reduction
Glutathione
Carcinogenesis
Proteins
Calcium
Lipids
Enzymes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer. / Erdelyi, Ildiko; Levenkova, Natasha; Lin, Elaine; Pinto, John T.; Lipkin, Martin; Quimby, Fred W.; Holt, Peter R.

In: Journal of Nutrition, Vol. 139, No. 11, 11.2009, p. 2072-2078.

Research output: Contribution to journalArticle

Erdelyi, Ildiko ; Levenkova, Natasha ; Lin, Elaine ; Pinto, John T. ; Lipkin, Martin ; Quimby, Fred W. ; Holt, Peter R. / Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer. In: Journal of Nutrition. 2009 ; Vol. 139, No. 11. pp. 2072-2078.
@article{a8cbe4f93f284da0bf9cfe6c9d5ecc3e,
title = "Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer",
abstract = "A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.",
author = "Ildiko Erdelyi and Natasha Levenkova and Elaine Lin and Pinto, {John T.} and Martin Lipkin and Quimby, {Fred W.} and Holt, {Peter R.}",
year = "2009",
month = "11",
doi = "10.3945/jn.108.104125",
language = "English (US)",
volume = "139",
pages = "2072--2078",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "11",

}

TY - JOUR

T1 - Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer

AU - Erdelyi, Ildiko

AU - Levenkova, Natasha

AU - Lin, Elaine

AU - Pinto, John T.

AU - Lipkin, Martin

AU - Quimby, Fred W.

AU - Holt, Peter R.

PY - 2009/11

Y1 - 2009/11

N2 - A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.

AB - A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.

UR - http://www.scopus.com/inward/record.url?scp=70350306941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350306941&partnerID=8YFLogxK

U2 - 10.3945/jn.108.104125

DO - 10.3945/jn.108.104125

M3 - Article

VL - 139

SP - 2072

EP - 2078

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 11

ER -