hooligosaccharide protein glycosyltransferase subunit 4. Given the high economic impact of IPN in salmonid culture, iden tification not of genes potentially involved in the progres sion of the disease using transcriptomic approaches is already in progress. Finally, down regulation of mal, associated with T cell differentiation and signal transduc tion, was observed at higher n 3 LC PUFA levels. As mentioned above, several immune response related genes were also affected by the total lipid factor with results validated by RT qPCR. However, we cannot exclude the possibility that this results from the strong correlation between total lipid levels and absolute LC PUFA contents, which makes it difficult to dissociate both factors.
Conclusions It has been demonstrated earlier that LC PUFA flesh content is a highly heritable trait, but the present study has shown that the underlying mechanisms do not appear to involve changes in the expression of lipid me tabolism genes, including the LC PUFA biosynthesis pathway. Other possible mechanisms, such as alleles with different biological activity, require investigation. The present study revealed an association between flesh adi posity and n 3 LC PUFA in the regulation of cholesterol biosynthesis, which was down regulated by higher n 3 LC PUFA levels but only in the lean families. This re sponse was not caused by dietary factors, given that the fish were all fed the same VO based diet, and is most likely explained by variation in tissue n 3 LC PUFA levels, regulating transcription of cholesterol metabolism genes through srebp2.
Furthermore, the transcriptional repression of these genes may be sensitive to the abso lute levels of these fatty acids in the tissues, which could explain the lack of regulation when comparing the fami lies containing higher flesh lipid levels. It is likely that n 3 LC PUFA exert similar roles in regulation of gene expression in fish as in mammals and, furthermore, fish might be a useful model to study important relation ships between genetics, diet, adiposity obesity and lipo protein cholesterol Cilengitide metabolism. However, unexpected differences were found in the expression of genes impli cated in the modulation of inflammatory processes and innate immune response between families differing in lipid composition, both in terms of total lipid level and, particularly, n 3 LC PUFA contents.
Although the evi protein inhibitor dence is generally circumstantial it is important to clarify this association if flesh n 3 LC PUFA level is included as a trait for genetic selection in Atlantic salmon breeding programmes. If such a relationship is confirmed, the data suggest that the underlying mechanism might involve anti inflammatory actions of tissue n 3 LC PUFA on the eicosanoid biosynthesis pathway, although direct effects through regulation of transcription of immune genes or more indirectly through changes in architecture and properties of immune cell membranes are also possible. Methods Feeding trial and sampling Fift