title: Intake of farmed Atlantic salmon fed soybean oil increases hepatic levels of arachidonic acid-derived oxylipins and ceramides in mice.
abstract: Introduction of vegetable ingredients in fish feed has affected the fatty acid composition in farmed Atlantic salmon (Salmo salar L). Here we investigated how changes in fish feed affected the metabolism of mice fed diets containing fillets from such farmed salmon. We demonstrate that replacement of fish oil with rapeseed oil or soybean oil in fish feed had distinct spillover effects in mice fed western diets containing the salmon. A reduced ratio of n-3/n-6 polyunsaturated fatty acids in the fish feed, reflected in the salmon, and hence also in the mice diets, led to a selectively increased abundance of arachidonic acid in the phospholipid pool in the livers of the mice. This was accompanied by increased levels of hepatic ceramides and arachidonic acid-derived pro-inflammatory mediators and a reduced abundance of oxylipins derived from eicosapentaenoic acid and docosahexaenoic acid. These changes were associated with increased whole body insulin resistance and hepatic steatosis. Our data suggest that an increased ratio between n-6 and n-3-derived oxylipins may underlie the observed marked metabolic differences between mice fed the different types of farmed salmon. These findings underpin the need for carefully considering the type of oil used for feed production in relation to salmon farming.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Lisa Kolden
authors.initials: LK
authors.lastname: Midtbø
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; Massachusetts General Hospital, Center for Computational and Integrative Biology, Boston, MA, USA; Obesity and Metabolism Research Unit, United States Department of Agriculture - Agricultural Research Service, Western Human Nutrition Research Center, CA, USA.
authors.forename: Alison G
authors.initials: AG
authors.lastname: Borkowska
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Annette
authors.initials: A
authors.lastname: Bernhard
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Alexander Krokedal
authors.initials: AK
authors.lastname: Rønnevik
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Lock
authors.affiliation: Massachusetts General Hospital, Center for Computational and Integrative Biology, Boston, MA, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Fitzgerald
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Bente E
authors.initials: BE
authors.lastname: Torstensen
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Liaset
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Brattelid
authors.affiliation: Obesity and Metabolism Research Unit, United States Department of Agriculture - Agricultural Research Service, Western Human Nutrition Research Center, CA, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Pedersen
authors.affiliation: Obesity and Metabolism Research Unit, United States Department of Agriculture - Agricultural Research Service, Western Human Nutrition Research Center, CA, USA; Department of Nutrition, University of California, Davis, USA; West Coast Metabolomics Center, University of California, Davis, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark. Electronic address: kk@bio.ku.dk.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway. Electronic address: lise.madsen@nifes.no.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000821:Animal Feed; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002518:Ceramides / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D066273:Diet, Western; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D005395:Fish Oils / Q000008:administration & dosage; D005989:Glycerides / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D054883:Oxylipins / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D020317:Salmo salar; D017747:Seafood; D013024:Soybean Oil / Q000008:administration & dosage*; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000410:Alanine Transaminase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D002135:Calcium-Binding Proteins; D002518:Ceramides; D018932:Chemokine CCL2; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D063388:Endocannabinoids; D005227:Fatty Acids; D005395:Fish Oils; D005989:Glycerides; D007328:Insulin; D054883:Oxylipins; D053284:Polyunsaturated Alkamides; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013024:Soybean Oil; D048069:Tumor Necrosis Factors; C000634132:Adgre1 protein, mouse; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse; C094503:glyceryl 2-arachidonate; C078814:anandamide
keywords: Aquaculture; DHA; Diabetes; EPA; Lipidomics; Obesity