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9 Publications visible to you, out of a total of 9

Abstract (Expand)

Atlantic salmon (Salmo salar) is the most valuable farmed fish globally and there is much interest in optimizing its genetics and rearing conditions for growth and feed efficiency. Marine feed ingredients must be replaced to meet global demand, with challenges for fish health and sustainability. Metabolic models can address this by connecting genomes to metabolism, which converts nutrients in the feed to energy and biomass, but such models are currently not available for major aquaculture species such as salmon. We present SALARECON, a model focusing on energy, amino acid, and nucleotide metabolism that links the Atlantic salmon genome to metabolic fluxes and growth. It performs well in standardized tests and captures expected metabolic (in)capabilities. We show that it can explain observed hypoxic growth in terms of metabolic fluxes and apply it to aquaculture by simulating growth with commercial feed ingredients. Predicted limiting amino acids and feed efficiencies agree with data, and the model suggests that marine feed efficiency can be achieved by supplementing a few amino acids to plant- and insect-based feeds. SALARECON is a high-quality model that makes it possible to simulate Atlantic salmon metabolism and growth. It can be used to explain Atlantic salmon physiology and address key challenges in aquaculture such as development of sustainable feeds.

Authors: Maksim Zakhartsev, Filip Rotnes, Marie Gulla, Ove Oyas, Jesse van Dam, Maria Suarez Diez, Fabian Grammes, Robert Hafthorsson, Wout van Helvoirt, Jasper Koehorst, Peter Schaap, Yang Jin, Liv Torunn Mydland, Arne Gjuvsland, Sandve Simen, Vitor Martins dos Santos, Jon Olav Vik

Date Published: 1st Jun 2022

Publication Type: Journal

Abstract (Expand)

Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long chain fatty acyl elongases (Elovls) and fatty acyl desaturases (Fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 partial knockout (KO), we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and that endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2-KOs showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-KO salmon showed accumulation of 20:4n-6 in brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of endogenous PUFA synthesis in Atlantic salmon.

Authors: Alex K. Datsomor, Nikola Zic, Keshuai Li, Rolf E. Olsen, Yang Jin, Jon Olav Vik, Rolf B. Edvardsen, Fabian Grammes, Anna Wargelius, Per Winge

Date Published: 1st Dec 2019

Publication Type: Not specified

Abstract (Expand)

Zebrafish is a useful modeling organism for the study of vertebrate development, immune response, and metabolism. Metabolic studies can be aided by mathematical reconstructions of the metabolic network of zebrafish. These list the substrates and products of all biochemical reactions that occur in the zebrafish. Mathematical techniques such as flux-balance analysis then make it possible to predict the possible metabolic flux distributions that optimize, for example, the turnover of food into biomass. The only available genome-scale reconstruction of zebrafish metabolism is ZebraGEM. In this study, we present ZebraGEM 2.0, an updated and validated version of ZebraGEM. ZebraGEM 2.0 is extended with gene-protein-reaction associations (GPRs) that are required to integrate genetic data with the metabolic model. To demonstrate the use of these GPRs, we performed an in silico genetic screening for knockouts of metabolic genes and validated the results against published in vivo genetic knockout and knockdown screenings. Among the single knockout simulations, we identified 74 essential genes, whose knockout stopped growth completely. Among these, 11 genes are known have an abnormal knockout or knockdown phenotype in vivo (partial), and 41 have human homologs associated with metabolic diseases. We also added the oxidative phosphorylation pathway, which was unavailable in the published version of ZebraGEM. The updated model performs better than the original model on a predetermined list of metabolic functions. We also determined a minimal feed composition. The oxidative phosphorylation pathways were validated by comparing with published experiments in which key components of the oxidative phosphorylation pathway were pharmacologically inhibited. To test the utility of ZebraGEM2.0 for obtaining new results, we integrated gene expression data from control and Mycobacterium marinum-infected zebrafish larvae. The resulting model predicts impeded growth and altered histidine metabolism in the infected larvae.

Authors: L. van Steijn, F. J. Verbeek, H. P. Spaink, R. M. H. Merks

Date Published: 20th Jun 2019

Publication Type: Not specified

Abstract (Expand)

The objective of this study was to evaluate the suitability of the rainbow trout intestinal epithelial cell line (RTgutGC) as an in vitro model for studies of gut immune function and effects of functional feed ingredients. Effects of lipopolysaccharide (LPS) and three functional feed ingredients [nucleotides, mannanoligosaccharides (MOS), and beta-glucans] were evaluated in RTgutGC cells grown on conventional culture plates and transwell membranes. Permeation of fluorescently-labeled albumin, transepithelial electrical resistance (TEER), and tight junction protein expression confirmed the barrier function of the cells. Brush border membrane enzyme activities [leucine aminopeptidase (LAP) and maltase] were detected in the RTgutGC cells but activity levels were not modulated by any of the exposures. Immune related genes were expressed at comparable relative basal levels as these in rainbow trout distal intestine. LPS produced markedly elevated gene expression levels of the pro-inflammatory cytokines il1b, il6, il8, and tnfa but had no effect on ROS production. Immunostaining demonstrated increased F-actin contents after LPS exposure. Among the functional feed ingredients, MOS seemed to be the most potent modulator of RTgutGC immune and barrier function. MOS significantly increased albumin permeation and il1b, il6, il8, tnfa, and tgfb expression, but suppressed ROS production, cell proliferation and myd88 expression. Induced levels of il1b and il8 were also observed after treatment with nucleotides and beta-glucans. For barrier function related genes, all treatments up-regulated the expression of cldn3 and suppressed cdh1 levels. Beta-glucans increased TEER levels and F-actin content. Collectively, the present study has provided new information on how functional ingredients commonly applied in aquafeeds can affect intestinal epithelial function in fish. Our findings suggest that RTgutGC cells possess characteristic features of functional intestinal epithelial cells indicating a potential for use as an efficient in vitro model to evaluate effects of bioactive feed ingredients on gut immune and barrier functions and their underlying cellular mechanisms.

Authors: Jie Wang, Peng Lei, Amr Ahmed Abdelrahim Gamil, Leidy Lagos, Yang Yue, Kristin Schirmer, Liv Torunn Mydland, Margareth Overland, Åshild Krogdahl, Trond M. Kortner

Date Published: 6th Feb 2019

Publication Type: Journal

Abstract (Expand)

Factors affecting the establishment of the gut microbiota in animals living in marine environments remain largely unknown. In terrestrial animals, however, it is well established that the juvenile environment has a major impact on the gut microbiota later in life. Atlantic salmon Salmo salar is an anadromous fish important in aquaculture with a juvenile freshwater stage and an adult seawater stage. For wild salmon, there are major dietary changes with respect to availability of long-chain polyunsaturated n-3 fatty acids (LC-n-3 PUFA) with lower abundance in freshwater systems. The aim of our work was therefore to determine the effect of a juvenile freshwater diet with high LC-n-3 PUFA, as compared to a diet low in LC-n-3 PUFA (designed to increase the endogenous LC-n-3 PUFA production), on the transition to a seawater gut microbiota for Atlantic salmon. We found a juvenile freshwater microbiota high in Firmicutes for fish raised with low LC-n-3 PUFA, while the microbiota for fish given high LC-n-3 PUFA feed was high in Proteobacteria. One hundred days after transfer to a common sea cage, fish that were given low LC-n-3 PUFA diets in freshwater showed significantly higher (p = 0.02, Kruskal-Wallis) Mycoplasma content (90 ± 7%; mean ± SD) compared to fish raised on a high LC-n-3 PUFA diet in freshwater (25 ± 31% Mycoplasma). Shotgun metagenome sequencing from fish raised with a low LC-n-3 PUFA diet identified a salmon-associated Mycoplasma in sea, being distinct from currently known Mycoplasma. The genome sequence information indicated a mutualistic lifestyle of this bacterium. Mycoplasma has also previously been identified as dominant (>70%) in sea-living adult Atlantic salmon. Taken together, our results suggest that the juvenile freshwater diet influences the establishment of the gut microbiota in marine Atlantic salmon.

Authors: Y Jin, IL Angell, SR Sandve, LG Snipen, Y Olsen, K Rudi

Date Published: 24th Jan 2019

Publication Type: Not specified

Abstract (Expand)

The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

Authors: S. Lien, B. F. Koop, S. R. Sandve, J. R. Miller, M. P. Kent, T. Nome, T. R. Hvidsten, J. S. Leong, D. R. Minkley, A. Zimin, F. Grammes, H. Grove, A. Gjuvsland, B. Walenz, R. A. Hermansen, K. von Schalburg, E. B. Rondeau, A. Di Genova, J. K. Samy, J. Olav Vik, M. D. Vigeland, L. Caler, U. Grimholt, S. Jentoft, D. Inge Vage, P. de Jong, T. Moen, M. Baranski, Y. Palti, D. R. Smith, J. A. Yorke, A. J. Nederbragt, A. Tooming-Klunderud, K. S. Jakobsen, X. Jiang, D. Fan, Y. Hu, D. A. Liberles, R. Vidal, P. Iturra, S. J. Jones, I. Jonassen, A. Maass, S. W. Omholt, W. S. Davidson

Date Published: 18th Apr 2016

Publication Type: Not specified

Abstract

Not specified

Authors: J. G. Caporaso, J. Kuczynski, J. Stombaugh, K. Bittinger, F. D. Bushman, E. K. Costello, N. Fierer, A. G. Pena, J. K. Goodrich, J. I. Gordon, G. A. Huttley, S. T. Kelley, D. Knights, J. E. Koenig, R. E. Ley, C. A. Lozupone, D. McDonald, B. D. Muegge, M. Pirrung, J. Reeder, J. R. Sevinsky, P. J. Turnbaugh, W. A. Walters, J. Widmann, T. Yatsunenko, J. Zaneveld, R. Knight

Date Published: 11th Apr 2010

Publication Type: Not specified

Abstract (Expand)

Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.

Authors: A. Brazma, P. Hingamp, J. Quackenbush, G. Sherlock, P. Spellman, C. Stoeckert, J. Aach, W. Ansorge, C. A. Ball, H. C. Causton, T. Gaasterland, P. Glenisson, F. C. Holstege, I. F. Kim, V. Markowitz, J. C. Matese, H. Parkinson, A. Robinson, U. Sarkans, S. Schulze-Kremer, J. Stewart, R. Taylor, J. Vilo, M. Vingron

Date Published: 1st Dec 2001

Publication Type: Not specified

Abstract (Expand)

Atlantic salmon migrates from rivers to sea to feed, grow and develop gonads before returning to spawn in freshwater. The transition to marine habitats is associated with dramatic changes in the environment, including water salinity, exposure to pathogens, and shift in dietary lipid availability. Many changes in physiology and metabolism occur across this life-stage transition, but little is known about the molecular nature of these changes. Here we use a long term feeding experiment to study transcriptional regulation of lipid metabolism in Atlantic salmon gut and liver in both fresh- and saltwater. We find that lipid metabolism becomes significantly less plastic to differences in dietary lipid composition when salmon transitions to saltwater and experiences increased dietary lipid availability. Expression of genes in liver relating to lipogenesis and lipid transport decrease overall and become less responsive to diet, while genes for lipid uptake in gut become more highly expressed. Finally, analyses of evolutionary consequences of the salmonid specific whole-genome duplication on lipid metabolism reveals several pathways with significantly different (p<0.05) duplicate retention or duplicate regulatory conservation. We also find a limited number of cases where the whole genome duplication has resulted in an increased gene dosage. In conclusion, we find variable and pathway-specific effects of the salmonid genome duplication on lipid metabolism genes. A clear life-stage associated shift in lipid metabolism regulation is evident, and we hypothesize this to be, at least partly, driven by non-dietary factors such as the preparatory remodeling of gene regulation and physiology prior to sea migration. This article is protected by copyright. All rights reserved.

Authors: G. Gillard, T. N. Harvey, A. Gjuvsland, Y. Jin, M. Thomassen, S. Lien, M. Leaver, J. S. Torgersen, T. R. Hvidsten, J. O. Vik, S. R. Sandve

Date Published: No date defined

Publication Type: Not specified

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