Effect of fatty acids and programming on the immune system

Abstract

Research to date has suggested that fatty acids (FAs) may affect the immune system, through their (and those of their metabolites) effects on membranes, mediators, and gene expression. However, despite the research carried out, there still exist gaps of knowledge where further research is required. In addition, programming by diet in pregnancy may affect the immune system, due to stress and/or structural and functional changes to immune cells, but whether this effect is long-lasting is uncertain. In order to address some of these gaps in knowledge, experiments were conducted to examine the effects of dietary FAs on immune outcomes in rodent models of clinical relevance and the effect of maternal protein restriction on immune outcomes in two later generations. The first experiment investigated the effect of diets differing in FA composition on the recall response in a mouse model of influenza vaccination. A diet rich in salmon oil resulted in enhanced ear swelling (measured after 48 hours) compared with diets rich in linseed oil, sunflower oil or beef tallow, suggesting that long chain n-3 FAs increase the TH1 response. The different effects of salmon oil compared with the other diets appears to relate to the lower n-6 fatty acid status that occurs with salmon oil feeding. The second experiment investigated the effect of diets differing in FA composition in a mouse model of allergic sensitisation (to ovalbumin). There was reduced immediate hypersensitivity to ovalbumin in mice fed a diet rich in salmon oil and increased immediate hypersensitivity in mice fed a diet rich in beef tallow, but there was no effect of diet on airway responsiveness to ovalbumin. Beef tallow feeding also raised IgE in blood and elevated IL-4 production by anti-CD3 stimulated splenocytes. The salmon oil did not affect IgE or cytokine profiles. The results suggest that the n-3 FAs found in salmon oil decrease TH2-mediated responses to an allergen and that such responses are increased by a diet rich in saturated FAs. The third experiment examined the effect of diets differing in FA composition fed during rat pregnancy on the abundance of different immune cells in blood and lymphoid organs of the offspring at weaning and beyond. The FA profile of the dams at the end of lactation reflected dietary intake in pregnancy, but no changes were found in immune cell abundance of offspring. The fourth experiment examined the effect of diets rich in a- linolenic acid (ALA, a short chain n-3 FA) or linoleic acid (LA, a short chain n-6 FA) in mouse pregnancy on allergic sensitisation to ovalbumin in the offspring. Diets were given during pregnancy alone, in both gestation and lactation, or during lactation alone, and compared to a low-fat control. The ALA-rich diet in gestation and lactation and the LArich diet in gestation reduced ear swelling in the offspring. Despite these differences, there were no effects on lung function or immune markers. The fifth experiment investigated the effect of protein restriction in rat pregnancy on the immune system of the offspring over two generations. No differences were seen between groups in the F1 generation. Protein restriction reduced TH and B-cell abundance in the spleen and thymus of F2 males. In conclusion, dietary fatty acids can alter immune responses, and there may be an effect of FAs in pregnancy on the immune response in the offspring but such effects may not be long lasting. Protein restriction during pregnancy, which is stress inducing, appears to have an effect on immune cell abundance that is manifested at the second generation of offspring

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ORCID for Philip C. Calder: orcid.org/0000-0002-6038-710X

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