Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals

Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace eco- logically 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

Molecular mechanism of dietary phospholipid requirement of Atlantic salmon, Salmo salar, fry

The phospholipid (PL) requirement in fish is revealed by enhanced performance when larvae are provided PL-enriched diets. To elucidate the molecular mechanism underlying PL requirement in Atlantic salmon, Salmo salar, were fed a minimal PL diet and tissue samples from major lipid metabolic sites were dissected from fry and parr. In silico analysis and cloning techniques demonstrated that salmon possess a full set of enzymes for the endogenous production of PL. The gene expression data indicated that major PL biosynthetic genes of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn) and phosphatidylinositol (PtdIns) display lower expression in intestine during the early developmental stage (fry). This is consistent with the hypothesis that the intestine of salmon is immature at the early developmental stage with limited capacity for endogenous PL biosynthesis. The results also indicate that intact PtdCho, PtdEtn and PtdIns are required in the diet at this stage. PtdCho and sphimgomyelin constitute the predominant PL in chylomicrons, involved in the transport of dietary lipids from the intestine to the rest of the body. As sphingomyelin can be produced from PtdCho in intestine of fry, our findings suggest that supplementation of dietary PtdCho alone during early developmental stages of Atlantic salmon would be sufficient to promote chylomicron formation. This would support efficient transport of dietary lipids, including PL precursors, from the intestine to the liver where biosynthesis of PtdEtn, PtdSer, and PtdIns is not compromised as in intestine facilitating efficient utilisation of dietary energy and the endogenous production of membrane PL for the rapidly growing and developing animal

Coronary steal by left atrial myxoma: a case report

This report describes a 41-year-old man who had atypical angina resulting from coronary steal by left atrial myxoma. The tumor was completely excised and the patient was symptoms free after operation

Influence of Development and Dietary Phospholipid Content and Composition on Intestinal Transcriptome of Atlantic Salmon (Salmo salar)

The inclusion of intact phospholipids in the diet is essential during larval development and can improve culture performance of many fish species. The effects of supplementation of dietary phospholipid from marine (krill) or plant (soy lecithin) sources were investigated in Atlantic salmon,Salmo salar. First feeding fry were fed diets containing either krill oil or soybean lecithin supplying phospholipid at 2.6%, 3.2%, 3.6% and 4.2% of diet. Fish were sampled at ~ 2.5 g (~1,990°day post fertilization, dpf) and ~10 g (2,850°dpf). By comparison of the intestinal transcriptome in specifically chosen contrasts, it was determined that by 2,850°dpf fish possessed a profile that resembled that of mature and differentiated intestinal cell types with a number of changes specific to glycerophospholipid metabolism. It was previously shown that intact phospholipids and particularly phosphatidylcholine are essential during larval development and that this requirement is associated with the inability of enterocytes in young fry to endogenously synthesize sufficient phospholipid for the efficient export of dietary lipid. In the immature phase (~1,990°dpf), the dietary phospholipid content as well as its class composition impacted on several biochemical and morphological parameters including growth, but these differences were not associated with differences in intestinal transcriptomes. The results of this study have made an important contribution to our understanding of the mechanisms associated with lipid transport and phospholipid biosynthesis in early life stages of fish

Improved fillet quality in harvest-size Atlantic salmon fed high n-3 canola oil as a DHA-source

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Monitoring the influence of marine aquaculture on wild fish communities: benefits and limitations of fatty acid profiles

Fatty acids (FA) have been applied as indicators of the influence of coastal sea-cage fish farming on wild fish communities in several recent scientific publications. Due to the relatively high conservation of FA composition throughout the food web, they are useful for characterizing trophic relationships. The increasing utilization of vegetable or alternative animal oils in the production of aquafeeds results in cultivated fish exhibiting higher levels of terrestrial FAs in their tissues. As previously reported, wild fish ubiquitously aggregate around fish farms as a consequence of the introduction of new habitat and the easy availability of food—fish farms act as enhanced fish aggregation devices (FADs). The influence of food pellets on the composition of wild fish has been detected in recent studies on salmon, sea bass and sea bream aquaculture, with increased levels of linoleic acid (18:2n-6) and a low n-3/n-6 ratio as clear indicators of the consumption of food pellets from the farms. The potential ecological and physiological effects on wild fish are presently unknown. In the present article, guidelines are proposed for the investigation and use of terrestrial FAs to track the effects of coastal aquaculture on wild fish communities and local fisheries, as well as the benefits or limitations of this technique

Atrial fibrosis identification with unipolar electrogram eigenvalue distribution analysis in multi-electrode arrays

Atrial fbrosis plays a key role in the initiation and progression of atrial fbrillation (AF). Atrial fbrosis is typically identifed by a peak-to-peak amplitude of bipolar electrograms (b-EGMs) lower than 0.5 mV, which may be considered as ablation targets. Nevertheless, this approach disregards signal spatiotemporal information and b-EGM sensitivity to catheter orientation. To overcome these limitations, we propose the dominant-to-remaining eigenvalue dominance ratio (EIGDR) of unipolar electrograms (u-EGMs) within neighbor electrode cliques as a waveform dispersion measure, hypothesizing that it is correlated with the presence of fbrosis. A simulated 2D tissue with a fbrosis patch was used for validation. We computed EIGDR maps from both original and time-aligned u-EGMs, denoted as R and RA, respectively, also mapping the gain in eigenvalue concentration obtained by the alignment, ΔRA. The performance of each map in detecting fbrosis was evaluated in scenarios including noise and variable electrode-tissue distance. Best results were achieved by RA, reaching 94% detection accuracy, versus the 86% of b-EGMs voltage maps. The proposed strategy was also tested in real u-EGMs from fbrotic and non-fbrotic areas over 3D electroanatomical maps, supporting the ability of the EIGDRs as fbrosis markers, encouraging further studies to confrm their translation to clinical settings

Internal mammary artery dilatation in a patient with aortic coarctation, aortic stenosis, and coronary disease. Case report

The ideal surgical approach is unclear in adult patients with coarctation of the aorta that is associated with other cardiovascular pathologies that require intervention. Standard median sternotomy allows simultaneous, coronary revascularization surgery, valve replacement and repair of aortic coarctation. However the collateral circulation and the anatomy of the mammary arteries must be determined, to avoid possible complications. We report a case of a 69 year-old man with aortic coarctation, aortic stenosis, coronary artery disease and internal mammary artery dilatation who underwent concomitant surgical procedures through a median sternotomy

Influence of dietary phospholipid on early development and performance of Atlantic salmon (Salmo salar)

The present study aimed to confirm the requirement for dietary phospholipid in Atlantic salmon and better define the level and period of requirement. Thus, the effects of dietary supplementation with phospholipid supplied by krill or soy lecithin were investigated in Atlantic salmon, Salmo salar. First feeding fry were fed diets containing 55 % protein and 17 % lipid supplemented with krill oil or soybean lecithin in a regression design at five levels, 1.5 (unsupplemented), 2.6, 3.2, 3.6 and 4.2 % total phospholipid and fish were sampled at 1 g (1400 ˚day post fertilisation, dpf), 2.5 g (1990 ˚dpf), 5 g (2350 ˚dpf), 10-20 g (2850 ˚dpf) and smolt (3800 ˚dpf). Survival was high overall with a positive correlation (r2 = 0.59 - 0.72) between survival and dietary phospholipid supplementation. Growth was improved by phospholipid with highest growth achieved in fish fed krill phospholipid at 2.6 % and in fish fed soy lecithin at 3.6 %. The pattern of growth differed between fish up to 2.5 g and that from 2.5 g onwards with SGR (0-2.5 g) being significantly higher in fish fed 2.6 % krill phospholipid and 3.6 % soy phospholipid compared to the basal diet, whereas there was no difference in SGR (2.5g-smolt) between the treatments. Intestinal steatosis was observed in 2.5 g fish fed the unsupplemented diet (20 % prevalence) and lower levels of soy (10 % prevalence), whereas it was absent from 2.5 g fish fed krill oil and higher levels of soy lecithin (≥ 3.2 %), and fish at all later stages. Prevalence of vertebral deformities was low but was reduced by increasing dietary phospholipid with krill oil generally being more effective. The results were consistent with salmon having a dietary requirement for dietary phospholipid in early life stages

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes

Aplastic anemia; DNA repair; Pulmonary fibrosisAnèmia aplàstica; Reparació d'ADN; Fibrosi pulmonarAnemia aplástica; Reparación de ADN; Fibrosis pulmonarBACKGROUND: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. METHODS: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. RESULTS: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening. CONCLUSION: Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed.Funded by grants PI14–01495 and PI17–01401 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain supported by FEDER funds) and by one ACCI project from CIBERER and one grant to the FPI cohort from CIBERES