Atlantic salmon (Salmo salar L.) sterol metabolism and metabolic health – impact of dietary lipids

Marine resources are today limited, and due to this there is an increasing inclusion of non-marine lipids in the diet of farmed salmonids. An optimal diet for farmed Atlantic salmon (Salmo salar L.) should not only promote fast growth, but also keep the fish at good health, making it robust to face changes and stressors from the surrounding environment. There is, however, still knowledge lacking about the nutritional needs of Atlantic salmon. Lipid sources vary in their fatty acid (FA) composition, as well as in content of other lipid soluble compounds, such as sterols and environmental contaminants. The focus of this thesis has been to study the effect of FAs and lipid soluble compounds on Atlantic salmon lipid metabolism and metabolic health. Very long-chained n-3 polyunsaturated fatty acids (VLC n-3 PUFAs), typically found in the marine environment, have on several occasions shown to have lipid-lowering properties. The lower dietary and tissue concentrations of these FAs in Atlantic salmon due to the substitution of marine oils with terrestrial oils, may thus have effects on the lipid metabolism. This was studied by performing four dietary trials using feeds with low concentrations of marine oils (0 – 86 g marine oils kg-1 feed), and thus also low dietary concentrations of VLC n-3 PUFAs (1.5 - 8.5 % eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) of total FAs and 0.5 – 6.6 % of diet). Lower dietary concentrations of VLC n-3 PUFAs tended to increase liver lipids in all the dietary trials. However, the observed changes in liver lipid content could not solely be explained by dietary concentrations of VLC n-3 PUFAs. Thus, dietary concentrations of saturated fats or plant sterols, commonly known as phytosterols, are hypothesised to affect liver lipid stores. Phytosterols are well-known to lower the uptake and synthesis of cholesterol, and might therefore have caused a cholesterol deficiency in the fish fed the low-marine diets containing low cholesterol levels. The transcription factors affected by phytosterols in the tissues are also involved in processes of lipogenesis, and disturbances in sterol metabolism could therefore affect the lipid storage in the liver. The effects of SFAs could not be separated from the effects of phytosterols with the current experimental designs. Thus, low dietary EPA and DHA concentrations (<2 % of diet) increased the risk of higher lipid depositions in the liver and changes in lipid metabolism. The magnitude of liver lipid levels were further elevated when low dietary concentrations of EPA and DHA were combined with high dietary phytosterols (1100 mg kg-1) and low saturated fat (<5 % of diet). The VLC n-3 PUFAs are also potent inhibitors of inflammation, and thus help maintaining a balanced function of the inflammatory system. Decreasing the concentrations of dietary VLC n-3 PUFAs and simultaneously increasing dietary concentrations of the pro-inflammatory n-6 FAs, common in vegetable oils, might skew the balance of the inflammatory system leading to a chronic low-grade inflammation. Temperature-dependant changes in inflammatory status were seen in Atlantic salmon fed very low dietary concentrations of VLC n-3 PUFAs (0.5 % EPA + DHA of diet), indicating dietary EPA and DHA below the minimum requirement for the fish to maintain an optimal inflammatory status. However, no effects on the response to a bacterial infection in vitro or on adiposity were seen due to the low dietary concentrations of VLC n-3 PUFAs or n-3/n-6 ratios as low as 1 to 0.3. Concomitant with changes in lipid composition, are the changes in environmental contaminants delivered via the diet when fish oil is replaced by vegetable oils. Many of these contaminants are highly lipid soluble, enabling them to bioaccumulate in the lipid portion of organisms. The same physical properties enable them to be embedded in biological membranes, where they can perturb the structure, and thus also the function, of the membranes. An increased fluidity of model membranes was observed when adding two different types of typical vegetable oil contaminants, polyaromatic hydrocarbons (PAHs). Some of the observed toxic effect of these compounds on fish could therefore be partially due to this membrane perturbing effect of the PAHs. The combined effect of non-optimal concentrations of various lipids and lipid soluble compounds might thus negatively affect the health of Atlantic salmon by affecting the liver lipid metabolism as well as inflammation and the physico-chemical properties of the lipid bilayer