Dataset Information

Daily rhythms in expression of genes of hepatic lipid metabolism in Atlantic salmon (Salmo salar L.).

ABSTRACT: In mammals, several genes involved in liver lipid and cholesterol homeostasis are rhythmically expressed with expression shown to be regulated by clock genes via Rev-erb 1?. In order to elucidate clock gene regulation of genes involved in lipid metabolism in Atlantic salmon (Salmo salar L.), the orphan nuclear receptor Rev-erb 1? was cloned and 24 h expression of clock genes, transcription factors and genes involved in cholesterol and lipid metabolism determined in liver of parr acclimated to a long-day photoperiod, which was previously shown to elicit rhythmic clock gene expression in the brain. Of the 31 genes analysed, significant daily expression was demonstrated in the clock gene Bmal1, transcription factor genes Srebp1, Lxr, Ppar? and Ppar?, and several lipid metabolism genes Hmgcr, Ipi, ApoCII and El. The possible regulatory mechanisms and pathways, and the functional significance of these patterns of expression were discussed. Importantly and in contrast to mammals, Per1, Per2, Fas, Srebp2, Cyp71? and Rev-erb 1? did not display significant daily rhythmicity in salmon. The present study is the first report characterising 24 h profiles of gene expression in liver of Atlantic salmon. However, more importantly, the predominant role of lipids in the nutrition and metabolism of fish, and of feed efficiency in determining farming economics, means that daily rhythmicity in the regulation of lipid metabolism will be an area of considerable interest for future research in commercially important species.

SUBMITTER: Betancor MB

PROVIDER: S-EPMC4153669 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Daily rhythms in expression of genes of hepatic lipid metabolism in Atlantic salmon (Salmo salar L.).

Betancor Mónica B MB McStay Elsbeth E Minghetti Matteo M Migaud Hervé H Tocher Douglas R DR Davie Andrew A

PloS one 20140903 9

In mammals, several genes involved in liver lipid and cholesterol homeostasis are rhythmically expressed with expression shown to be regulated by clock genes via Rev-erb 1α. In order to elucidate clock gene regulation of genes involved in lipid metabolism in Atlantic salmon (Salmo salar L.), the orphan nuclear receptor Rev-erb 1α was cloned and 24 h expression of clock genes, transcription factors and genes involved in cholesterol and lipid metabolism determined in liver of parr acclimated to a ...[more]

PMID: 25184355

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Project description:BACKGROUND: Uranium (U) is a naturally occurring radionuclide that has been found in the aquatic environment due to anthropogenic activities. Exposure to U may pose risk to aquatic organisms due to its radiological and chemical toxicity. The present study aimed to characterize the chemical toxicity of U in Atlantic salmon (Salmo salar) using depleted uranium (DU) as a test model. The fish were exposed to three environmentally relevant concentrations of DU (0.25, 0.5 and 1.0 mg U/L) for 48 h. Hepatic transcriptional responses were studied using microarrays in combination with quantitative real-time reverse transcription polymerase chain reaction (qPCR). Plasma variables and chromosomal damages were also studied to link transcriptional responses to potential physiological changes at higher levels. RESULTS: The microarray gene expression analysis identified 847, 891 and 766 differentially expressed genes (DEGs) in the liver of salmon after 48 h exposure to 0.25, 0.5 and 1.0 mg/L DU, respectively. These DEGs were associated with known gene ontology functions such as generation of precursor metabolites and energy, carbohydrate metabolic process and cellular homeostasis. The salmon DEGs were then mapped to mammalian orthologs and subjected to protein-protein network and pathway analysis. The results showed that various toxicity pathways involved in mitochondrial functions, oxidative stress, nuclear receptor signaling, organ damage were commonly affected by all DU concentrations. Eight genes representative of several key pathways were further verified using qPCR No significant formation of micronuclei in the red blood cells or alterations of plasma stress variables were identified. CONCLUSION: The current study suggested that the mitochondrion may be a key target of U chemical toxicity in salmon. The induction of oxidative stress and uncoupling of oxidative phosphorylation may be two potential modes of action (MoA) of DU. These MoAs may subsequently lead to downstream events such as apoptosis, DNA repair, hypoxia signaling and immune response. The early toxicological mechanisms of U chemical toxicity in salmon has for the first time been systematically profiled. However, no other physiological changes were observed. Future efforts to link transcriptional responses to adverse effects have been outlined as important for understanding of potential risk to aquatic organisms.

Project description: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.

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Dataset Information

Daily rhythms in expression of genes of hepatic lipid metabolism in Atlantic salmon (Salmo salar L.).

Publications

Daily rhythms in expression of genes of hepatic lipid metabolism in Atlantic salmon (Salmo salar L.).

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