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. 2016 Jun 1;310(11):G906-19.
doi: 10.1152/ajpgi.00345.2015. Epub 2016 Mar 31.

High-fat Diets Rich in Saturated Fat Protect Against Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer

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Free PMC article

High-fat Diets Rich in Saturated Fat Protect Against Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer

Reilly T Enos et al. Am J Physiol Gastrointest Liver Physiol. .
Free PMC article

Abstract

High-fat-diet (HFD) consumption is associated with colon cancer risk. However, little is known about how the lipid composition of a HFD can influence prooncogenic processes. We examined the effects of three HFDs differing in the percentage of total calories from saturated fat (SF) (6, 12, and 24% of total caloric intake), but identical in total fat (40%), and a commercially available Western diet (26 and 41% saturated and total fat, respectively) on colon cancer development using the azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model. A second dose-response experiment was performed using diets supplemented with the saturated-fatty-acid (SFA)-rich coconut oil. In experiment 1, we found an inverse association between SF content and tumor burden. Furthermore, increased SF content was associated with reduced inflammation, increased apoptosis, and decreased proliferation. The second dose-response experiment was performed to test whether this effect may be attributed to the SF content of the diets. Consistent with the initial experiment, we found that high SF content was protective, at least in male mice; there was a decrease in mortality in mice consuming the highest concentration of SFAs. To explore a potential mechanism for these findings, we examined colonic mucin 2 (Muc2) protein content and found that the HFDs with the highest SF content had the greatest concentration of Muc2. Our data suggest that high dietary SF is protective in the AOM/DSS model of colon cancer, which may be due, at least in part, to the ability of SF to maintain intestinal barrier integrity through increased colonic Muc2.

Keywords: high-fat diet; inflammation; mucin 2.

Figures

Fig. 1.
Fig. 1.
Influence of the azoxymethane (AOM)/dextran sulfate sodium (DSS) model on body weights (A), symptom scores (B), mean symptom score data over the course of the study (C), and symptom score-tumor number correlational analysis (D) (n = 8–10/group). Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).
Fig. 2.
Fig. 2.
Tumor and colon inflammatory data from experiment 1. Shown are tumor burden (A), colon weight (B), colon length-to-width ratio (C), colon inflammatory markers (D), and representative colonic hematoxylin and eosin (H&E) images (E) (×20) of each treatment group (n = 8–10/group). SF, saturated fat; WD, Western diet. Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).
Fig. 3.
Fig. 3.
Activation of proteins regulating carcinogenesis. Shown are representative Western blots of colonic phosphorylated (p)-NF-κB p65 and total NF-κB (A), p-ERK ½ and total ERK ½ (B), p-p38 and total p38 (C), and p-STAT-3 and total STAT3 (D) (n = 4–9/group). IOD, intensity of densitometry. Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).
Fig. 4.
Fig. 4.
Apoptosis and proliferation. Shown are representative Western blots of colonic cleaved caspase 3 (A) and proliferating cell nuclear antigen (PCNA, B) (n = 5–9/group). Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).
Fig. 5.
Fig. 5.
Gut barrier integrity. Colonic mRNA expression and correlation to tumor number of mucin (Muc) 2 (A), Muc6 (B), and Muc5ac (C) (n = 8–10/group), as well as representative Western blot of colonic Muc2 (D) (n = 5–9/group) and colonic mRNA expression of tight junction protein 1 (TJP1) and occludin (E) (n = 8–10/group). Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).
Fig. 6.
Fig. 6.
Adipose tissue outcomes from experiment 1. Shown are body composition (A), visceral adipose tissue (B), adipose tissue inflammatory markers (C), glucose metabolism (E), and representative adipose tissue H&E images (×20) and F4/80 immunohistochemistry (D) (×40) of each treatment group (n = 10/group). Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).
Fig. 7.
Fig. 7.
Mortality data of males (A) and females (B) from experiment 2 (n = 10/group). Groups not sharing a common letter differ significantly from one another (P ≤ 0.05).

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