The effect of sesamin supplementation in vegetable oil enriched feed on the expression of microRNA in Atlantic salmon (Salmo salar L.)

Abstract: Fish is without doubt the most important source of valuable omega-3 (n-3) fatty acids (FA), especially the long chain polyunsaturated fatty acids (LCPUFA) eicosa-pentaenoic acid (EPA) and docosahexaenoic acid (DHA). Aquaculture production of Atlantic salmon (Salmo salar) is one of the largest fish industries in the world and a dominant source of fish in Western diet. Fish meal and fish oil (FO) are im-portant dietary components in fish feed and vital sources of nutrients and fatty acids in salmonid aquaculture. However, due to overfishing and high pressure on the aquatic ecosystem feeding the growing aquaculture industry have become a sustainability issue. To solve the issue, FO has increasingly been replaced with vegetable oils (VO). This has documented effects on the lipid profile of fish flesh e.g. by lowering the amount of the valuable omega-3 LCPUFAs. Nutrigenomic approaches have been used to try to increase the levels of LCPUFAs in Atlantic salmon as well as other salmonids fed VO diets by the addi-tion of bioactive compounds e.g. sesamin a bioactive compound extracted from sesame seeds. Sesamin has been shown to affect expression of genes involved in the lipid metabolism, but little is known about the underlying molecular regulation mechanism. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation and communication within as well as between cells. In-creased understanding of how miRNAs effect the regulation of lipid metabolism, specifically the desaturation and elongation cascade of omega-3 (n-3) and omega-6 (n-6) LCPUFAs, can contribute in the search for a more sustainable aquaculture. Understanding the role of miRNA and other small non-coding RNAs as well as other post-transcriptional regulation mechanisms might help in finding a sustainable feeding method without losing the nutritional value of the fish filé. The aim of this thesis is to investigate if genes involved in the lipid metabolism are under regulatory control of miRNAs in Atlantic salmon. Expression of 19 dif-ferent miRNAs were compared in Atlantic salmon fed different feeding profiles of VO that differ in n-6 to n-3 FA ratio (low or high) and sesamin content (high, low or no sesamin). The result indicates that miRNA most likely are a part of the feedback regulation mechanisms of lipid metabolism and that at least seven of the 18 miRNAt tested might regulate genes involved in the lipid homeostasis. Many mRNA showed a significant difference in expression levels in fish fed VO compared to the FO diet. Further, supplementation of sesamin to VO diet had a significant effect on the expression of several miRNAs. In many cases the addition of sesamin to the VO diet restored the miRNA expression to levels similar to that of fish fed the FO diet.