Differential regulation of colonic PPAR expression by dietary fatty acids

Hontecillas, R., S.C. Jobgen, L.L. Beary, M.J. Wannemuehler, and J. Bassaganya-Riera. (2003) Differential regulation of colonic PPAR expression by dietary fatty acids. The FASEB Journal 17(5): A1161 (Abstract #713.2).

Intestinal homeostasis is maintained by balanced immune and inflammatory responses, epithelial integrity, and lymphoepithelial cross-talk. Immune function, inflammation and epithelial survival can be nutritionally controlled by fatty acids and vitamins. Both endoplasmic and nuclear mechanisms mediate the actions of fatty acids on mucosal health. In regards to the nuclear mechanisms of transcriptional regulation, nuclear hormone receptors such as peroxisome proliferator-activated receptors (PPARs) are likely molecular targets for the anti-inflammatory actions of polyunsaturated fatty acids (PUFA). We previously demonstrated that dietary supplementation with conjugated linoleic acid (CLA) suppressed the expression of immunoregulatory cytokines (i.e., interferon-γ and interleukin-10) in draining lymph nodes and enhanced colonic PPAR-γ expression following the onset of colitis in pigs. These molecular changes correlated with decreased colonic inflammation. More recently we have used a dextran sodium sulfate (DSS)-induced colitis model to examine if the dietary PUFA composition affects PPAR expression in mice. We hypothesized that dietary CLA-supplementation increases PPAR-γ expression in mice following the onset of enteric disease. To test this hypothesis, pups were fed a basal AIN-93G diet in which 14.28 % of the soybean oil (i.e., 1 g/100g of diet) was replaced with either linoleic acid, linolenic acid, CLA, or docosahexanoic acid (DHA). Pups were challenged with 2.5% DSS in the drinking water and colonic samples were recovered at 7 days post-challenge. Expression of colonic PPAR-α, PPAR-γ1, PPAR-δ and PPAR-binding protein (PBP) was assayed using RT-PCR. Dietary CLA-supplementation upregulated PPAR-δ mRNA expression in inflamed colons whereas PPAR-α and PBP were upregulated in the linoleic acid-supplemented group. In contrast to the pig colons, inflamed mice colons expressed similar levels of PPAR-γ mRNA across diets. The enhanced colonic PPAR-δ expression in CLA-fed mice correlated with diminished weight loss and mucosal inflammation. Comparisons between the two animal models of inflammatory bowel disease suggest that the nutritional regulation of PPAR isoform expression by CLA may be species-specific.