Dietary Carbohydrate Source Alters Gene Expression Profile of Intestinal Epithelium in Mice

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824, USA.
Nutrition and Cancer (Impact Factor: 2.32). 02/2009; 61(1):146-55. DOI: 10.1080/01635580802372617
Source: PubMed


High-sucrose consumption is associated with increased risk of human colon cancer. Our previous research indicated that high-sucrose diets (vs. cornstarch) promote intestinal epithelial cell proliferation and tumorigenesis as well as increase serum glucose and hepatic IGF-I mRNA levels in APC(Min) mice. To examine the role of functional pathways, in particular of IGF-I signaling, in sucrose-induced intestinal epithelial cell proliferation and tumorigenesis, we examined the effects of dietary carbohydrate source (sucrose vs. cornstarch) on gene expression in the intestinal epithelium using cDNA microarray and quantitative RT-PCR analysis. Dietary carbohydrate source significantly (P < 0.05) altered mRNA expression of 109 known genes in the small intestinal epithelium, including many involved in metabolic pathways. Consumption of high-sucrose diets altered expression levels of genes involved in cell adhesion, cell cycle control, and transduction signaling, consistent with increased risk of intestinal tumorigenesis. High-sucrose intake also affected expression of genes involved in IGF-I signaling, including upregulating IGF-II and downregulating IGFBP3, which supports our hypothesis that IGF-I signaling could play a role in intestinal epithelial cell proliferation and tumorigenesis promoted by high-sucrose consumption.

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    ABSTRACT: Epidemiological studies report that high sucrose consumption is associated with increased risk of colon cancer. One hypothesis is that this association is mediated by elevated circulatory insulin and IGF levels promoting intestinal proliferation. To test this hypothesis, APC(Min) mice and their wild type littermates were fed, starting at 4 wk of age, sucrose or cornstarch as the sole carbohydrate source in the absence or presence of low levels of dietary sulindac for 10 or 16 wk, respectively. APC(Min) mice fed sucrose had an increased tumor number in the proximal third of the small intestine in both studies and a higher incidence of papillary colon tumors in the 16-wk feeding study (P < or = 0.05). Mice fed sucrose (relative to cornstarch) had higher body weights and greater Ki67-labeling indexes in colonic epithelium than mice fed cornstarch in both feeding studies (P < or = 0.05). Furthermore, mice fed sucrose had higher serum glucose and liver IGF-I mRNA concentrations (P < or = 0.05) and tended to have higher serum insulin levels (P = 0.08). These results support the hypothesis that high dietary sucrose intake promotes intestinal proliferation and tumorigenesis by increasing circulating levels of insulin and IGF-I.
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