title: Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals.
abstract: Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets.
authors.affiliation: School of Natural Sciences, University of Stirling, Institute of Aquaculture, Stirling FK9 4LA, UK. Electronic address: g.e.carmonaantonanzas@stir.ac.uk.
authors.forename: Greta
authors.initials: G
authors.lastname: Carmona-Antoñanzas
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Tocher
authors.forename: Laura
authors.initials: L
authors.lastname: Martinez-Rubio
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Leaver
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008322:Mammals / Q000235:genetics; D008954:Models, Biological; D012474:Salmon / Q000235:genetics* / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D029941:Fish Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D002784:Cholesterol
keywords: 3-hydroxy-3-methyl-glutaryl-CoA reductase; ABCA1; ACOX; ARA; ATP-binding cassette transporter 1; Atlantic salmon; CYP7α1; DHA; DMEM; DNA complementary to RNA; Dulbecco's modified eagle medium; EDTA; ELF-1α; ELOVL; EPA; ER; FA; FADS; FAS; FBS; FHM; FO; Fatty acid; Gene expression; HMG-CoAR; LBD; LC-PUFA; LO; LXR; LXR response element; LXRE; Lipid; ORF; PBS; PPAR; PPAR response element; PPRE; PUFA; Pyloric caeca; RE; RO; RXR; SCD; SHK-1; SO; SRE; SREBP; TF; Transcription factor; UAS; VO; aa; acyl-CoA oxidase; amino acid(s); arachidonic acid; base pair(s); bp; cDNA; cholesterol 7alpha-hydroxylase; docosahexaenoic acid; eicosapentaenoic acid; elongase of very long-chain fatty acids; elongation factor 1 alpha; endoplasmic reticulum; ethylenediaminetetraacetic acid; fathead minnow epithelial cells; fatty acid; fatty acid desaturase; fatty acid synthase; fetal bovine serum; fish oil; ligand binding domain; linseed oil; liver X receptor; long-chain polyunsaturated fatty acids; mRNA; messenger RNA; open reading frame; peroxisome proliferator-activated receptors; phosphate buffer saline; polyunsaturated fatty acids; qPCR; quantitative RT-PCR; rapeseed oil; response element; retinoid X receptor; salmon head kidney cells; serum response element; soybean oil; stearoyl CoA desaturase; sterol regulatory element binding proteins; transcription factor; upstream activation sequence; vegetable oil