Effect of Dietary Cholesterol, Phytosterol, and Docosahexaenoic Acid on Astaxanthin Absorption and Retention in Rainbow Trout.

Astaxanthin (Ax) determines the flesh redness of a salmonid fish which is the most desirable quality indicator by consumers. Fish cannot synthesize Ax de novo, therefore, the only way to increase flesh redness is to increase dietary input or improve the absorption and retention rate of dietary Ax. As a hydrophobic carotenoid, the absorption of Ax can be modulated by other lipid molecules in the diet.

A hierarchy of metabolite exchanges in metabolic models of microbial species and communities.

The metabolic network of an organism can be analyzed as a constraint-based model. This analysis can be biased, optimizing an objective such as growth rate, or unbiased, aiming to describe the full feasible space of metabolic fluxes through pathway analysis or random flux sampling. In particular, pathway analysis can decompose the flux space into fundamental and formally defined metabolic pathways.

The genome regulatory landscape of Atlantic salmon liver through smoltification.

The anadromous Atlantic salmon undergo a preparatory physiological transformation before seawater entry, referred to as smoltification. Key molecular developmental processes involved in this life stage transition, such as remodeling of gill functions, are known to be synchronized and modulated by environmental cues like photoperiod. However, little is known about the photoperiod influence and genome regulatory processes driving other canonical aspects of smoltification such as the large-scale changes in lipid metabolism and energy homeostasis in the developing smolt liver.

Extracting functionally accurate context-specific models of Atlantic salmon metabolism.

Constraint-based models (CBMs) are used to study metabolic network structure and function in organisms ranging from microbes to multicellular eukaryotes. Published CBMs are usually generic rather than context-specific, meaning that they do not capture differences in reaction activities, which, in turn, determine metabolic capabilities, between cell types, tissues, environments, or other conditions. Only a subset of a CBM's metabolic reactions and capabilities are likely to be active in any given context, and several methods have therefore been developed to extract context-specific models from generic CBMs through integration of omics data.

SALARECON connects the Atlantic salmon genome to growth and feed efficiency.

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.

Diet and Life Stage-Associated Lipidome Remodeling in Atlantic Salmon.

Salmon is an important source of long-chain highly unsaturated fatty acids (LC-HUFAs) such as 22:6-3 [docosahexaenoic acid (DHA)]. In the present study, we conducted two identical experiments on salmon in freshwater (FW) and seawater (SW) stages, with a diet switch from fish oil (high in LC-HUFA) to vegetable oil (low in LC-HUFA) and vice versa. Our aim was to investigate the diet and life stage-specific features of lipid uptake (gut), processing (liver), and deposition (muscle).

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

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.

Publisher Correction: MEMOTE for standardized genome-scale metabolic model testing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Empusa code generator and its application to GBOL, an extendable ontology for genome annotation.

The RDF data model facilitates integration of diverse data available in structured and semi-structured formats. To obtain a coherent RDF graph the chosen ontology must be consistently applied. However, addition of new diverse data causes the ontology to evolve, which could lead to accumulation of unintended erroneous composites.

Liver slice culture as a model for lipid metabolism in fish.

Hepatic lipid metabolism is traditionally investigated in vitro using hepatocyte monocultures lacking the complex three-dimensional structure and interacting cell types essential liver function. Precision cut liver slice (PCLS) culture represents an alternative in vitro system, which benefits from retention of tissue architecture. Here, we present the first comprehensive evaluation of the PCLS method in fish (Atlantic salmon, Salmo salar L.

CRISPR/Cas9-mediated ablation of elovl2 in Atlantic salmon (Salmo salar L.) inhibits elongation of polyunsaturated fatty acids and induces Srebp-1 and target genes.

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.

A systemic study of lipid metabolism regulation in salmon fingerlings and early juveniles fed plant oil.

In salmon farming, the scarcity of fish oil has driven a shift towards the use of plant-based oil from vegetable or seed, leading to fish feed low in long-chain PUFA (LC-PUFA) and cholesterol. Atlantic salmon has the capacity to synthesise both LC-PUFA and cholesterol, but little is known about the regulation of synthesis and how it varies throughout salmon life span. Here, we present a systemic view of lipid metabolism pathways based on lipid analyses and transcriptomic data from salmon fed contrasting diets of plant or fish oil from first feeding.

Transcriptional development of phospholipid and lipoprotein metabolism in different intestinal regions of Atlantic salmon (Salmo salar) fry.

Background: It has been suggested that the high phospholipid (PL) requirement in Atlantic salmon (Salmo salar) fry is due to insufficient intestinal de-novo synthesis causing low lipoprotein (LP) production and reduced transport capacity of dietary lipids. However, in-depth ontogenetic analysis of intestinal PL and LP synthesis with the development of salmon has yet to be performed. Therefore, in this paper we used RNA-Seq technology to investigate the expression of genes involved in PL synthesis and LP formation throughout early developmental stages and associate insufficient expression of synthesis pathways in salmon fry with its higher dietary PL requirement.

Life-stage-associated remodelling of lipid metabolism regulation in Atlantic salmon.

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.

Stable Core Gut Microbiota across the Freshwater-to-Saltwater Transition for Farmed Atlantic Salmon.

Gut microbiota associations through habitat transitions are fundamentally important yet poorly understood. One such habitat transition is the migration from freshwater to saltwater for anadromous fish, such as salmon. The aim of the current work was therefore to determine the freshwater-to-saltwater transition impact on the gut microbiota in farmed Atlantic salmon, with dietary interventions resembling freshwater and saltwater diets with respect to fatty acid composition.

Functional Annotation of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture.

We describe an emerging initiative - the 'Functional Annotation of All Salmonid Genomes' (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.

Towards causally cohesive genotype-phenotype modelling for characterization of the soft-tissue mechanics of the heart in normal and pathological geometries.

A scientific understanding of individual variation is key to personalized medicine, integrating genotypic and phenotypic information via computational physiology. Genetic effects are often context-dependent, differing between genetic backgrounds or physiological states such as disease. Here, we analyse in silico genotype-phenotype maps (GP map) for a soft-tissue mechanics model of the passive inflation phase of the heartbeat, contrasting the effects of microstructural and other low-level parameters assumed to be genetically influenced, under normal, concentrically hypertrophic and eccentrically hypertrophic geometries.

A call for virtual experiments: accelerating the scientific process.

Experimentation is fundamental to the scientific method, whether for exploration, description or explanation. We argue that promoting the reuse of virtual experiments (the in silico analogues of wet-lab or field experiments) would vastly improve the usefulness and relevance of computational models, encouraging critical scrutiny of models and serving as a common language between modellers and experimentalists. We review the benefits of reusable virtual experiments: in specifying, assaying, and comparing the behavioural repertoires of models; as prerequisites for reproducible research; to guide model reuse and composition; and for quality assurance in the translational application of models.

A computational pipeline for quantification of mouse myocardial stiffness parameters.

The mouse is an important model for theoretical-experimental cardiac research, and biophysically based whole organ models of the mouse heart are now within reach. However, the passive material properties of mouse myocardium have not been much studied. We present an experimental setup and associated computational pipeline to quantify these stiffness properties.

Effect of regulatory architecture on broad versus narrow sense heritability.

Additive genetic variance (VA ) and total genetic variance (VG ) are core concepts in biomedical, evolutionary and production-biology genetics. What determines the large variation in reported VA /VG ratios from line-cross experiments is not well understood. Here we report how the VA /VG ratio, and thus the ratio between narrow and broad sense heritability (h(2) /H(2) ), varies as a function of the regulatory architecture underlying genotype-to-phenotype (GP) maps.

Bridging the genotype-phenotype gap: what does it take?

The genotype-phenotype map (GP map) concept applies to any time point in the ontogeny of a living system. It is the outcome of very complex dynamics that include environmental effects, and bridging the genotype-phenotype gap is synonymous with understanding these dynamics. The context for this understanding is physiology, and the disciplinary goals of physiology do indeed demand the physiological community to seek this understanding.

Parameters in dynamic models of complex traits are containers of missing heritability.

Polymorphisms identified in genome-wide association studies of human traits rarely explain more than a small proportion of the heritable variation, and improving this situation within the current paradigm appears daunting. Given a well-validated dynamic model of a complex physiological trait, a substantial part of the underlying genetic variation must manifest as variation in model parameters. These parameters are themselves phenotypic traits.