title: High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer.
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.
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
authors.forename: Reilly T
authors.initials: RT
authors.lastname: Enos
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
authors.forename: Kandy T
authors.initials: KT
authors.lastname: Velázquez
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: McClellan
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Cranford
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, South Carolina.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Davis
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina; and Angela.Murphy@uscmed.sc.edu.
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
mesh_terms: D000818:Animals; D017209:Apoptosis; D001397:Azoxymethane / Q000633:toxicity; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000178:diet therapy* / Q000209:etiology / Q000517:prevention & control; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000627:therapeutic use; D005227:Fatty Acids / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D012967:Sodium Dodecyl Sulfate; D001397:Azoxymethane
keywords: high-fat diet; inflammation; mucin 2