title: EPA, DHA, and Lipoic Acid Differentially Modulate the n-3 Fatty Acid Biosynthetic Pathway in Atlantic Salmon Hepatocytes.
abstract: The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1-14C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1-14C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion. DHA production, on the other hand, was maintained even in groups with high endogenous levels of DHA, possibly due to a more complex regulation of this last step in the n-3 metabolic pathway. Inhibition of the Δ6 desaturase pathway led to increased direct elongation to 20:3n-3 by both DHA and LA. Possibly the route by 20:3n-3 and then Δ8 desaturation to 20:4n-3, bypassing the first Δ6 desaturase step, can partly explain the maintained or even increased levels of DHA production. LA increased DHA production in the phospholipid fraction of hepatocytes isolated from fish fed 0 and 0.5% EPA and/or DHA, indicating that LA has the potential to further increase the production of this health-beneficial FA in fish fed diets with low levels of EPA and/or DHA.
authors.affiliation: Nofima (Norwegian Institute of Food, Fisheries and Aquaculture Research), P.O. Box 210, 1431, Ås, Norway. marta.bou@nofima.no.|Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, Norway. marta.bou@nofima.no.
authors.forename: Marta
authors.initials: M
authors.lastname: Bou
authors.affiliation: Nofima (Norwegian Institute of Food, Fisheries and Aquaculture Research), P.O. Box 210, 1431, Ås, Norway.
authors.forename: Tone-Kari
authors.initials: TK
authors.lastname: Østbye
authors.affiliation: Nofima, 6600, Sunndalsøra, Norway.
authors.forename: Gerd M
authors.initials: GM
authors.lastname: Berge
authors.affiliation: Nofima (Norwegian Institute of Food, Fisheries and Aquaculture Research), P.O. Box 210, 1431, Ås, Norway.|Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Ruyter
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000096:biosynthesis; D015118:Eicosapentaenoic Acid / Q000096:biosynthesis; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000494:pharmacology; D029941:Fish Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020317:Salmo salar / Q000378:metabolism*; D008063:Thioctic Acid / Q000096:biosynthesis; D017962:alpha-Linolenic Acid / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D015525:Fatty Acids, Omega-3; D029941:Fish Proteins; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D008063:Thioctic Acid; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases
keywords: Desaturases; Elongases; Fatty acid metabolism; Fish nutrition; In vitro; n-3 fatty acids