Apolipocrustacein, formerly vitellogenin, is the major egg yolk precursor protein in decapod crustaceans and is homologous to insect apolipophorin II/I and vertebrate apolipoprotein B

BACKGROUND: In animals, the biogenesis of some lipoprotein classes requires members of the ancient large lipid transfer protein (LLTP) superfamily, including the cytosolic large subunit of microsomal triglyceride transfer protein (MTP), vertebrate apolipoprotein B (apoB), vitellogenin (Vtg), and insect apolipophorin II/I precursor (apoLp-II/I). In most oviparous species, Vtg, a large glycolipoprotein, is the main egg yolk precursor protein. RESULTS: This report clarifies the phylogenetic relationships of LLTP superfamily members and classifies them into three families and their related subfamilies. This means that the generic term Vtg is no longer a functional term, but is rather based on phylogenetic/structural criteria. In addition, we determined that the main egg yolk precursor protein of decapod crustaceans show an overall greater sequence similarity with apoLp-II/I than other LLTP, including Vtgs. This close association is supported by the phylogenetic analysis, i.e. neighbor-joining, maximum likelihood and Bayesian inference methods, of conserved sequence motifs and the presence of three common conserved domains: an N-terminal large lipid transfer module marker for LLTP, a DUF1081 domain of unknown function in their central region exclusively shared with apoLp-II/I and apoB, and a von Willebrand-factor type D domain at their C-terminal end. Additionally, they share a conserved functional subtilisin-like endoprotease cleavage site with apoLp-II/I, in a similar location. CONCLUSION: The structural and phylogenetic data presented indicate that the major egg yolk precursor protein of decapod crustaceans is surprisingly closely related to insect apoLp-II/I and vertebrate apoB and should be known as apolipocrustacein (apoCr) rather than Vtg. These LLTP may arise from an ancient duplication event leading to paralogs of Vtg sequences. The presence of LLTP homologs in one genome may facilitate redundancy, e.g. involvement in lipid metabolism and as egg yolk precursor protein, and neofunctionalization and subfunctionalization, e.g. involvement in clotting cascade and immune response, of extracellular LLTP members. These protein-coding nuclear genes may be used to resolve phylogenetic relationships among the major arthropod groups, especially the Pancrustacea-major splits

Analyse in vivo de la dynamique du tissu adipeux blanc après exposition à des polluants chimiques ou à des molécules pharmacologiques chez le poisson zèbre

Un régime alimentaire déséquilibré et/ou la présence de composés contaminantsexogènes peuvent modifier la signalisation endocrine et l homéostasie des lipides et induirel obésité. Les travaux réalisés dans le cadre de cette thèse ont permis, dans un premier temps,de développer une méthode simple et rapide, dénommée "zebrafish obesogenic (ZO) test",pour identifier in vivo, par utilisation de la larve de poisson zèbre, des facteurs qui peuventaugmenter ou diminuer la taille de l adipocyte blanc et ainsi moduler le niveau de l adiposité(Tingaud-Sequeira, Ouadah, Babin, J. Lipid Res. 52, 1765-1772, 2011). Ce test permetd identifier des composés et des mélanges de molécules obésogènes et anti-obésogènes etfournit des informations pertinentes pour l'évaluation des risques liés leur présence maiségalement pour élucider les mécanismes impliqués. Les travaux ont, dans un second temps,permis d apporter des réponses quant aux modalités d action d un obésogène puissant, lechlorure de tributylétain, contaminant retrouvé très largement dans notre environnement.Cette molécule agit sur l adipocyte blanc à une concentration de l ordre du nano molaire viales récepteurs nucléaires RXR et LXR, et non pas via les isoformes PPARgamma/delta(Ouadah et Babin, manuscrit en préparation).An unbalanced diet and / or the presence of exogenous compounds contaminants mayalter endocrine signaling and lipid homeostasis and induce obesity. The work done in thisthesis have, at first, developed a simple and rapid method, called "zebrafish obesogenic (ZO)test" to identify in vivo by using the zebrafish larva, the factors that may increase or decreasethe size of the white adipocyte and therefore modulate the level of adiposity (Tingaud-Sequeira, Ouadah, Babin, J. Lipid Res. 52, 1765-1772, 2011). This test helps to identifycompounds and mixtures of obesogenic and anti-obesogenic molecules and providesinformation relevant to the risk assessment of their presence but also to elucidate themechanisms involved. Work in a second time allowed to answer as to how the action oftributyltin chloride, a powerful obesogenic contaminant found widely in the environment.This molecule acts in vivo on white adipocytes in a concentration of the order of nano molarvia nuclear receptors LXR and RXR, and not via the PPARgamma isoforms / delta (Ouadahand Babin, manuscript in preparation).BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Proximal aortic stiffening in Turner patients may be present before dilation can be detected : a segmental functional MRI study

Background: To study segmental structural and functional aortic properties in Turner syndrome (TS) patients. Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome. Cardiovascular magnetic resonance (CMR) allows segmental study of aortic elastic properties. Method: We performed Pulse Wave Velocity (PWV) and distensibility measurements using CMR of the thoracic and abdominal aorta in 55 TS-patients, aged 13-59y, and in a control population (n = 38; 12-58y). We investigated the contribution of TS on aortic stiffness in our entire cohort, in bicuspid (BAV) versus tricuspid (TAV) aortic valve-morphology subgroups, and in the younger and older subgroups. Results: Differences in aortic properties were only seen at the most proximal aortic level. BAV Turner patients had significantly higher PWV, compared to TAV Turner (p = 0.014), who in turn had significantly higher PWV compared to controls (p = 0.010). BAV Turner patients had significantly larger ascending aortic (AA) luminal area and lower AA distensibility compared to both controls (all p < 0.01) and TAV Turner patients. TAV Turner had similar AA luminal areas and AA distensibility compared to Controls. Functional changes are present in younger and older Turner subjects, whereas ascending aortic dilation is prominent in older Turner patients. Clinically relevant dilatation (TAV and BAV) was associated with reduced distensibility. Conclusion: Aortic stiffening and dilation in TS affects the proximal aorta, and is more pronounced, although not exclusively, in BAV TS patients. Functional abnormalities are present at an early age, suggesting an aortic wall disease inherent to the TS. Whether this increased stiffness at young age can predict later dilatation needs to be studied longitudinally

Molecular phenotype of zebrafish ovarian follicle by serial analysis of gene expression and proteomic profiling, and comparison with the transcriptomes of other animals

BACKGROUND: The ability of an oocyte to develop into a viable embryo depends on the accumulation of specific maternal information and molecules, such as RNAs and proteins. A serial analysis of gene expression (SAGE) was carried out in parallel with proteomic analysis on fully-grown ovarian follicles from zebrafish (Danio rerio). The data obtained were compared with ovary/follicle/egg molecular phenotypes of other animals, published or available in public sequence databases. RESULTS: Sequencing of 27,486 SAGE tags identified 11,399 different ones, including 3,329 tags with an occurrence superior to one. Fifty-eight genes were expressed at over 0.15% of the total population and represented 17.34% of the mRNA population identified. The three most expressed transcripts were a rhamnose-binding lectin, beta-actin 2, and a transcribed locus similar to the H2B histone family. Comparison with the large-scale expressed sequence tags sequencing approach revealed highly expressed transcripts that were not previously known to be expressed at high levels in fish ovaries, like the short-sized polarized metallothionein 2 transcript. A higher sensitivity for the detection of transcripts with a characterized maternal genetic contribution was also demonstrated compared to large-scale sequencing of cDNA libraries. Ferritin heavy polypeptide 1, heat shock protein 90-beta, lactate dehydrogenase B4, beta-actin isoforms, tubulin beta 2, ATP synthase subunit 9, together with 40 S ribosomal protein S27a, were common highly-expressed transcripts of vertebrate ovary/unfertilized egg. Comparison of transcriptome and proteome data revealed that transcript levels provide little predictive value with respect to the extent of protein abundance. All the proteins identified by proteomic analysis of fully-grown zebrafish follicles had at least one transcript counterpart, with two exceptions: eosinophil chemotactic cytokine and nothepsin. CONCLUSION: This study provides a complete sequence data set of maternal mRNA stored in zebrafish germ cells at the end of oogenesis. This catalogue contains highly-expressed transcripts that are part of a vertebrate ovarian expressed gene signature. Comparison of transcriptome and proteome data identified downregulated transcripts or proteins potentially incorporated in the oocyte by endocytosis. The molecular phenotype described provides groundwork for future experimental approaches aimed at identifying functionally important stored maternal transcripts and proteins involved in oogenesis and early stages of embryo development

Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models

Some natural products, known sources of bioactive compounds with a wide range of properties, may have therapeutic values in human health and diseases, as well as agronomic applications. The effect of three compounds of plant origin with well-known dietary antioxidant properties, astaxanthin (ATX), caffeic acid (CA) and hydroxytyrosol (HT), on zebrafish (Danio rerio) larval adiposity and rainbow trout (Onchorynchus mykiss) adipocytes was assessed. The zebrafish obesogenic test (ZOT) demonstrated the anti-obesogenic activity of CA and HT. These compounds were able to counteract the obesogenic effect produced by the peroxisome proliferator-activated receptor gamma (PPAR.) agonist, rosiglitazone (RGZ). CA and HT suppressed RGZ-increased PPAR. protein expression and lipid accumulation in primary-cultured rainbow trout adipocytes. HT also significantly reduced plasma triacylglycerol concentrations, as well as mRNA levels of the fasn adipogenic gene in the adipose tissue of HT-injected rainbow trout. In conclusion, in vitro and in vivo approaches demonstrated the anti-obesogenic potential of CA and HT on teleost fish models that may be relevant for studying their molecular mode of action. Further studies are required to evaluate the effect of these bioactive components as food supplements for modulating adiposity in farmed fish

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei

Intracellular lipid binding proteins, including fatty acid binding proteins (FABPs) 1 and 2, are highly expressed in tissues involved in the active lipid metabolism. A zebrafish model was used to demonstrate differential expression levels of fabp1b.1, fabp1b.2, and fabp2 transcripts in liver, anterior intestine, and brain. Transcription levels of fabp1b.1 and fabp2 in the anterior intestine were upregulated after feeding and modulated according to diet formulation. Immunofluorescence and electron microscopy immunodetection with gold particles localized these FABPs in the microvilli, cytosol, and nuclei of most enterocytes in the anterior intestinal mucosa. Nuclear localization was mostly in the interchromatin space outside the condensed chromatin clusters. Native PAGE binding assay of BODIPY-FL-labeled FAs demonstrated binding of BODIPY-FLC12 but not BODIPY-FLC5 to recombinant Fabp1b.1 and Fabp2. The binding of BODIPY-FLC12 to Fabp1b.1 was fully displaced by oleic acid. In vivo experiments demonstrated, for the first time, that intestinal absorption of dietary BODIPY-FLC12 was followed by colocalization of the labeled FA with Fabp1b and Fabp2 in the nuclei. These data suggest that dietary FAs complexed with FABPs are able to reach the enterocyte nucleus with the potential to modulate nuclear activity