Establishing the essentiality of fats in the postnatal diet for optimal development

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The overall goal of my NSERC program is to establish the essentiality of dietary fats for immunity in the early postnatal period. We will study 3 specific fats,,docosahexaenoic acid (DHA), arachidonic acid (AA) and phosphatidylcholine (PC), for which a supply is needed by the immune system, but they are not currently considered essential in the diet. The suckling period and the weaning period are both critical stages when the immune system matures and the animal develops oral tolerance (OT), the ability to distinguish between harmful and harmless oral antigens. We have demonstrated that adding DHA or PC to otherwise nutritionally adequate diets improves immune maturation and function. ******During the next 5y, my NSERC program will focus on 4 objectives:***1) Establishing the dietary essentiality of AA during immune development ***2) Optimizing dietary AA/DHA ratio for immune development ***3) Establishing the amount of PC in the diet for immune development, then using this PC to deliver/improve the supply of long chain polyunsaturated fatty acids (LCPUFA) to immune cells ***4) Identifying the change in plasma and immune phospholipids (PL) as a biomarker of intake******Using male and female Sprague-Dawley and allergen sensitive Brown Norway rats, we will study how changes in the AA, DHA/AA ratio and the PC content of the diet influence immune function during suckling and weaning. For the suckling studies we will change pups' intake through changing their dams' diets. For testing the essentiality of AA (below levels in breast milk) we will use an artificial rearing model. OT will be studied using methods that induce systemic or mucosal tolerance to the food protein ovalbumin (OVA). After inducing OT, plasma concentrations of OVA-specific IgE and IgG are measured. Immune cells are isolated from the spleen and characterized (by flow cytometry) then used to assess their ability to produce cytokines (Th1 or Th2 pattern) to normal physiological challenges' using mitogens or OVA. By measuring the change in plasma, breast milk, immune cell PL (content, fatty acid composition) and choline (content, composition) we propose to identify biomarkers that predict immune function and will provide targets for developing a novel PC supplement.******Hypothesizes: 1) AA is required; 2) a ratio of 1:2 (AA:DHA) will optimize immune maturation; 3) choline coming from free choline and PC (25:75) is optimal; and 4) the content and fatty acid composition of plasma PC will be an ideal biomarker to monitor LCPUFA status associated with optimal immune development.******This fundamental knowledge is needed to establish the dietary need of these lipids for immune development. Additionally, we will identify biomarkers that predict immune function and develop a PC supplement to provide all 3 lipids. My NSERC program will contribute to the unique training of different types of HPQ in the field of nutritional immunology.