Final Report Summary - FISHINUTRIGEN (Fish intestinal nutrigenomics in response to fish oil replacement in Atlantic salmon diets) The overall objectives of the FISHINUTRIGEN project were to promote sustainable development of European aquaculture. Marine aquaculture, which provides an increasing quantity of affordable and nutritious fish for human consumption, relies heavily on fish meal (FM) and fish oil (FO) from wild stocks for the production of fish feeds. However, this practice is ecologically unsound and unsustainable given the worldwide reduction in fisheries landings. Therefore, the lack of FO supply may seriously limit aquaculture growth and the future of this activity strongly depends on its replacement with alternative oils. Vegetable oils (VO) present a high potential in this respect. Nonetheless, VO, which can be rich in C18 polyunsaturated fatty acids (PUFA), are devoid of the n-3 long chain PUFA (LC-PUFA), such as EPA and DHA, which are abundant in FO. Thus, growth of fish on VO results in lower levels of n-3 LC-PUFA in their flesh, compromising their nutritional value and health-promoting effects to the human consumer. Thus, a major thrust of this project was to determine the effects of sustainable diets for Atlantic salmon (i.e. replacing FO and FM by vegetable alternatives - VO and VM), in conjunction with genotype (different families) variation, on gene (microarray and RT-qPCR) and protein (proteomics) expression. The main objectives were to: 1) identify the molecular pathways underpinning the adaptation to VO diets and 2) determine whether different families may vary in their capacity to deposit and retain n-3 LC-PUFA in their flesh, when fed VO diets deficient in these fatty acids and, ultimately, if this is a trait that might be genetically selected for. The underlying idea is that combining genetic selection with changes in commercial diet formulations (inclusion of higher levels of VO) might be a viable strategy to meet worldwide growing demands for aquaculture products, minimising losses in fish welfare and nutritional value. This project was coordinated by Prof. Douglas Tocher (email@example.com) and conducted by Dr Sofia Morais within the Molecular nutrition group at the Institute of Aquaculture, University of Stirling (see http://www.aqua.stir.ac.uk/ online), as part of the EU FP6 IP Aquamax - Sustainable aquafeeds to maximise the health benefits of farmed fish for consumers (016249-2) (see http://www.aquamaxip.eu/files/Aquamax%20Fact%20sheet.pdf online).An experiment was performed in which two groups of Atlantic salmon from families with different fat deposition phenotypes ('fat' versus 'lean') were fed experimental diets containing 25 % FM and 44 % VM and either 100 % FO or 100 % VO. The effect of these diets on gene expression (transcriptome) in the liver and intestine, as well as on protein expression (proteome) in intestine, was examined in both families. The results clearly indicate that different salmon families react differently, in terms of their liver and intestinal transcriptome, as well as their intestinal proteome, to dietary substitution of FO by VO. Concerning the intestinal transcriptome, the 'fat' family showed a higher response in terms of lipid metabolism-related genes to FO replacement by VO. In particular, a strong significant interaction was observed for genes that are involved in LC-PUFA biosynthesis from C18 fatty acid precursors, which are abundant in VO. This was the case for Δ6- and Δ5- desaturases and elongase (elovl2), which are widely known to be up-regulated in response to dietary FO replacement by VO in Atlantic salmon, as well as in other fish species. However, in this study, the response depended on the family, with 'lean' fish responding atypically, showing no regulation of these LC-PUFA biosynthesis genes, while in the 'fat' family we observed the typical response of previously studied salmon commercial lines. In liver, the diet change affected mostly metabolism-related genes, particularly those related to lipid metabolism and glucose and intermediary metabolism.