关键词： 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

Mesh ： Animals Cholesterol / metabolism Dietary Fats / metabolism Fatty Acids / metabolism Female Fish Proteins / genetics metabolism Gene Regulatory Networks Lipid Metabolism / genetics Male Mammals / genetics Models, Biological Salmon / genetics metabolism Sterol Regulatory Element Binding Protein 1 / genetics metabolism Transcription Factors / genetics metabolism Transcription, Genetic

来  源：   DOI：10.1016/j.gene.2013.10.040

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.
摘要：
由于最近努力取代生态有限的海洋成分，水产饲料中的脂质含量和组成发生了迅速变化，鱼粉和鱼油（FO）。陆地植物产品是最经济和可持续的替代品；然而，植物膳食和油缺乏生理上重要的胆固醇和长链多不饱和脂肪酸（LC-PUFA），二十碳五烯酸（EPA），二十二碳六烯酸（DHA）和花生四烯酸（ARA）。尽管用植物油（VO）代替膳食FO对大西洋鲑鱼（Salmosalar）的生长几乎没有影响，一些研究表明，对与脂质稳态有关的基因的活性和表达有重要影响。在脊椎动物中，固醇和LC-PUFA通过与脂质敏感转录因子（TFs）的直接相互作用以及靶基因的调控在脂质代谢中起关键作用。本研究的主要目的是通过TFs的转染和过表达来阐明关键TFs在鱼类脂质代谢转录调控中的作用。结果表明，LC-PUFA生物合成基因(elovl和fads2)和胆固醇代谢基因(abca1)的表达受鲑鱼Lxr和SrebpTFs的调控，表明脊椎动物之间高度保守的调控机制。此外,srebp1和srebp2mRNA对VO替代饮食FO有反应。因此，大西洋鲑鱼通过基因表达的转录调节调节脂质代谢以响应膳食脂质组成。通过在配制饮食时考虑这些重要的分子相互作用，有可能进一步提高水产养殖中海产品可持续替代品的效率和有效利用。
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