Establishing the Influence of Dietary Fatty Acids on the Colon through Nutrigenomics

  • Nelly Chankova

    Student thesis: Phd


    IntroductionThe fatty acid (FA) composition of the diet can have both a positive and negative impact on the health and wellbeing of an individual. Diets rich in saturated FAs and cholesterol promote cardiovascular disease, while diets rich in omega 3 FA protect against cardiovascular disease. Diets rich in omega 6 FAs are thought to have pro-inflammatory and promoting properties, while diets rich in omega 3 FAs have anti-inflammatory and chemo preventative qualities. The increase of the ratio of omega 6 to omega 3 FAs is an important factor in the increased incidence of inflammatory diseases such as inflammatory bowel disease, cancer, and heart disease. The aim of this project was to find how the different FA composition of the diet would affect the phenotype of healthy mice.MethodsC57BL6 mice were fed diets enriched with fish oil, safflower oil, or lard, in order to produce diets rich in omega 3 PUFAs (Fish oil - FO), omega 6 PUFAs (Safflower oil - SO) or saturated FA enriched (Lard). Colonic epithelial cells (CECs) were used to determine the length of time necessary to see changes in the FA profile measured with gas chromatography. Gas chromatography was used to determine the changes in the FA profile of whole ascending colon due to changes in the FA composition of the diet. An Affymetrix array experiment was done to look for changes in the transcriptome of the ascending colon in effect of the different composition of the diets used. Changes in the tight junction protein expression in the whole ascending were measured with western blotting and fluorescent immunohistochemistry.Main ResultsChanging the diet from standard maintenance chow to a high fat FO diet caused significant changes in the FAs composition of the CEC within 10 days. FO and SO diets produced mismatched changes in the omega 3 and omega 6 FAs, which caused a significant 4.8 fold increase of the omega 3/omega 6 FA ratio in the lipids extracted from mice fed the FO diet, and a small decrease in the lipids extracted from mice fed the SO diet. The diets employed produced only very small or negligible changes in the trasncriptome of the ascending colon. The diets did affect the expression of the tight junction proteins. Expression of claudin 2 and claudin 12 increased in the colons of all mice fed the experimental diets, although the increase was significant only in the samples from mice fed the lard enriched diet.ConclusionsModifying the dietary FA composition can cause significant changes in the FA profile of the colonic epithelium within 10 days and the ascending colon within 15 days. However, these changes had a negligible effect on the transcriptome of the ascending colon. The changes in the FA composition of the colon did, however, cause changes in the TJ protein expression depending on the FA composition of the diet. 
    Date of Award1 Aug 2013
    Original languageEnglish
    Awarding Institution
    • The University of Manchester
    SupervisorJohn Mclaughlin (Supervisor) & Philip Padfield (Supervisor)

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