Dataset Information

Targeted mutagenesis of ?5 and ?6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar).

ABSTRACT: BACKGROUND:With declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with other genes involved in lipid metabolism. Several key genes of LC-HUFA synthesis in salmon belong to the fatty acid desaturases 2 (fads2) family. The present study applied whole transcriptome analysis on two CRISPR-mutated salmon strains (crispants), 1) ?6abc/5Mt with mutations in ?5fads2, ?6fads2-a, ?6fads2-b and ?6fads2-c genes, and 2) ?6bcMt with mutations in ?6fads2-b and ?6fads2-c genes. Our purpose is to evaluate the genetic effect fads2 mutations have on other lipid metabolism pathways in fish, as well as to investigate mosaicism in a commercial species with a very long embryonal period. RESULTS:Both ?6abc/5Mt and ?6bcMt crispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. The ?6abc/5Mt fish displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation of srebp1 genes which are known key transcription regulators of lipid metabolism as well as a number of down-stream genes involved in fatty acid de-novo synthesis, fatty acid ?-oxidation and lipogenesis. Both elovl5 and elovl2 genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation of ?6bcMt surprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability. CONCLUSIONS:CRISPR-Cas9 can efficiently mutate multiple fads2 genes simultaneously in salmon. The results of the present study have provided new information on the transcriptional regulations of lipid metabolism genes after reduction of LC-HUFA synthesis pathways in salmon.

SUBMITTER: Jin Y

PROVIDER: S-EPMC7678299 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Targeted mutagenesis of ∆5 and ∆6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar).

Jin Yang Y Datsomor Alex K AK Olsen Rolf E RE Vik Jon Olav JO Torgersen Jacob S JS Edvardsen Rolf B RB Wargelius Anna A Winge Per P Grammes Fabian F

BMC genomics 20201119 1

<h4>Background</h4>With declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with ...[more]

PMID: 33213387

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Project description:Peracetic acid (PAA) is an organic peroxide that produces free radicals, which contribute to its potent disinfection power. At therapeutic doses, PAA is considered a mild stressor that can trigger transient local and systemic oxidative stress in fish, but the resulting consequences in the brain have yet to be identified. Therefore, we report the brain transcriptome of Atlantic salmon (Salmo salar) smolts that have been periodically exposed to PAA. Fish were treated three times (every 15 days) with PAA with either short (15 min) or long (30 min) exposure periods. After the third treatment, the whole brain was collected and subjected to biochemical and transcriptomic analyses. The level of reactive oxygen species in the brain was not significantly affected by recurrent PAA treatments. Microarray analysis was performed on the whole brain and revealed 205 differentially expressed genes (DEGs), regardless of the duration of the treatment. The short exposure duration had a more considerable impact on the brain transcriptome, correlating with 70% more DEGs than the long exposure. Strikingly, the brain transcriptome was characterised by the downregulation of gene expression, especially in the short exposure group, and around 82% of the identified DEGs were downregulated. Some of the highly affected genes were key molecules of the vasotocinergic and isotocinergic systems and the corticotropin-releasing factor signalling system, indicating interference of the stress axis but could also suggest an anxiolytic effect. In addition, there were alterations in genes involved in cellular metabolism and processing, signalling and trafficking, and innate immunity, which underscores the physiological changes in the brain following recurrent PAA treatment. Overall, the transcriptomic data reveal that recurrent oxidant treatment could influence brain functions, and although the magnitude was marginal, the alterations suggested neurological adaptations of fish to PAA as a potential chemical stressor. The results identify the risks of PAA, which would be valuable in drafting a framework for its empirically driven use in fish farming.

Project description:The high-affinity/low-capacity system Slc15a2 (PepT2) is responsible for the reuptake of di/tripeptides from the renal proximal tubule, but it also operates in many other tissues and organs. Information regarding PepT2 in teleost fish is limited and, to date, functional data are available from the zebrafish (Danio rerio) only. Here, we report the identification of two slc15a2 genes in the Atlantic salmon (Salmo salar) genome, namely slc15a2a and slc15a2b. The two encoded PepT2 proteins share 87% identity and resemble both structurally and functionally the canonical vertebrate PepT2 system. The mRNA tissue distribution analyses reveal a widespread distribution of slc15a2a transcripts, being more abundant in the brain and gills, while slc15a2b transcripts are mainly expressed in the kidney and the distal part of the gastrointestinal tract. The function of the two transporters was investigated by heterologous expression in Xenopus laevis oocytes and two-electrode voltage-clamp recordings of transport and presteady-state currents. Both PepT2a and PepT2b in the presence of Gly-Gln elicit pH-dependent and Na+ independent inward currents. The biophysical and kinetic analysis of the recorded currents defined the transport properties, confirming that the two Atlantic salmon PepT2 proteins behave as high-affinity/low-capacity transporters. The recent structures and the previous kinetic schemes of rat and human PepT2 qualitatively account for the characteristics of the two Atlantic salmon proteins. This study is the first to report on the functional expression of two PepT2-type transporters that operate in the same vertebrate organism as a result of (a) gene duplication process(es). KEY POINTS: Two slc15a2-type genes, slc15a2a and slc15a2b coding for PepT2-type peptide transporters were found in the Atlantic salmon. slc15a2a transcripts, widely distributed in the fish tissues, are abundant in the brain and gills, while slc15a2b transcripts are mainly expressed in the kidney and distal gastrointestinal tract. Amino acids involved in vertebrate Slc15 transport function are conserved in PepT2a and PepT2b proteins. Detailed kinetic analysis indicates that both PepT2a and PepT2b operate as high-affinity transporters. The kinetic schemes and structures proposed for the mammalian models of PepT2 are suitable to explain the function of the two Atlantic salmon transporters.

Dataset Information

Targeted mutagenesis of ?5 and ?6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar).

Publications

Targeted mutagenesis of ∆5 and ∆6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar).

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