Genome-Wide Analysis of Dietary Eicosapentaenoic Acid- and Oleic Acid-Induced Modulation of Colon Inflammation in Interleukin-10 Gene-Deficient Mice

Abstract

<i>Background/Aims:</i> Dietary n–3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient <i>(Il10</i><sup>–/–</sup><i>)</i> mice. <i>Methods:</i> At 35 days of age, 12 weaned <i>Il10</i><sup>–/–</sup> and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n–3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. <i>Results:</i> In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed <i>Il10</i><sup>–/–</sup> compared to C57 mice. <i>Il10</i><sup>–/–</sup> mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in <i>Il10</i><sup>–/–</sup> mice. <i>Conclusions:</i> These data indicate that dietary EPA-induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the <i>Ppara</i> gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins.