Circulating anthocyanin metabolites mediate vascular benefits of blueberries:insights from randomized controlled trials, metabolomics, and nutrigenomics

Potential health benefits of blueberries may be due to vascular effects of anthocyanins which predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation (FMD). The effects were similar to those of blueberries containing similar amounts of anthocyanins while control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month blueberry consumption increased FMD and lowered 24h-ambulatory-systolic-blood-pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 17 correlated with acute and chronic FMD improvements, respectively. Injection of these metabolites improved FMD in mice. Daily blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs

Protéines de la matrice extracellulaire bovine et rôle potentiel dans la qualité de la viande : Premier recueil in silico Bos taurus

International audienceThe extracellular matrix (ECM) is a three-dimensional set of proteins that binds tissues and defines their biomechanical properties. Among the ECM components known to be involved in beef sensory qualities, authors have often studied fibrillar collagens but also, although less often, proteoglycans and some glycoproteins. The ECM contains many other proteins. Our hypothesis is that to deepen the role of ECM proteins in beef qualities and to identify new ones among the vast amount of data generated by high throughput methods, it is necessary to have a list of proteins of this matrix to refer to for the bovine species. We have therefore defined the Bos taurus matrisome known as the set of genes encoding ECM (core matrisome proteins and matrisome-associated proteins). We have used orthology, as a reference method, and a bioinformatic approach based on a computational pipeline previously published for Homo sapiens, Mus musculus and Danio rerio for the definition of their respective matrisome. We have reported here that the Bos taurus matrisome is composed of 1022 genes that we have classified according to the different matrisome categories. This list is the only matrisome of a livestock species to be defined to date. SIGNIFICANCE: In this study, we provide the first definition of matrisome of a livestock species, the Bos taurus. We believe that the Bos taurus matrisome will be of great interest for several reasons. It comes as a complement to the matrisomes of several other species such as Homo sapiens, Mus musculus, Danio rerio, Drosophila melanogaster and Caenorabditis elegans previously defined by other authors. It could be used to identify matrisome molecules among the vast amount of data generated by the high throughput methods. It thus can be used in addition to the other matrisomes as a model by the scientific community to study cell behavior and mechanotransduction and could lead to the identification of novel biomarkers for several diseases and cancers in which ECM is involved. Moreover, in the domain of studies on livestock, the dataset that we have provided here can be used in the context of product quality studies, especially meat quality, but also, for example, for lactation studies

Exploitation bioinformatique de la comparaison des transcriptomes de tissus adipeux de chèvres lactantes et non lactantes: Rapport de stage DUT Génie Biologique -BioInformatique 2ème Année 2015/2016

LicenceThe objective of this study was to compare the lipid storage mechanisms in adipose tissue of lactating goats (in phase of mobilization of fat reserves) and non-lactating (lipid storage phase). A high-throughput RNA sequencing (RNA-seq) extracted from adipose tissue showed that 252 genes were differentially expressed. We have exploited these results using several bioinformatics tools. A Gene Ontological (GO) analyzes allowed classifying these Differentially Expressed Genes (DEG) in 14 biological processes. Enrichment tests were then performed and revealed an enrichment of GO associated with lipid metabolism. Metabolic pathways and network construction enrichment tools have enabled us to identify the pathways of fatty acid and their degradation, specifically targeting two key regulators, leptin and HNF4A transcription factor. Thus, we were able to show that these DEG in the adipose tissue of dairy goats are mostly involved in oxidation and lipid synthesis. These results are just the first hypotheses and these analyses must be performed by confronting with zootechnic data and caprine annotations. The operating strategy of the data could be used for the analysis of new RNA-seqdata.Exploitation bioinformatique de la comparaison des transcriptomes de tissus adipeux de chèvres lactantes et non lactantesL’objectif de cette étude a été de comparer les mécanismes de stockage lipidique dans les tissus adipeux de chèvres lactantes (en phase de mobilisation des réserves lipidiques) et non lactantes (en phase de stockage lipidique). Un séquençage haut débit des ARN (RNA-seq) extraits du tissu adipeux a montré que 252 gènes étaient différentiellement exprimés (GDE). Nous avons exploité ces résultats à l’aide de plusieurs outils bio-informatiques. Une analyse Gene Ontologique (GO) a permis de classer ces GDE dans 14 processus biologiques. Des tests d’enrichissement ont mis en évidence un enrichissement des GO associés au métabolisme lipidique. Des outils d’enrichissement de voies métaboliques et de construction de réseaux nous ont ensuite permis d’identifier les pathways des acides gras et de leur dégradation en ciblant notamment deux régulateurs clés, la leptine et le facteur de transcription HNF4A. Nous avons ainsi pu mettre en évidence que ces GDE dans les tissus adipeux de chèvres laitières sont surtout impliqués dans l’oxydation et la synthèse des lipides. Ces résultats ne sont que des premières hypothèses et ces analyses devront être poursuivies en les confrontant aux données zootechniques et aux annotations caprines. Cette stratégie d’exploitation des données pourra servir à l’analyse de nouvelles données RNA-se

Plasma flavanol metabolites modulate expression of miRNA in endothelial cells and affect post-transcriptional regulation of genes regulating adhesion and transendothelial migration

National audienceMicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs and constitute a class of post-transcriptional regulators. We showed previously that flavanol metabolites decrease adhesion of monocytes to endothelial cells through modulation of expression of genes. The aim of this work was to identify the impact of flavanol metabolites at physiologically-relevant concentrations on the expression of miRNAs in endothelial cells. The use of microarrays revealed that 4’MEC, 4’MEC7G and EC4’S can modulate expression of miRNAs involved in the regulation of inflammation, cell adhesion or cell invasion, such as miR-221 or miR-181. These metabolites regulate the expression of different miRNAs that could exert post-transcriptional regulation of different target genes that are however involved in the same cellular pathways. These pathways mainly concern those involved in regulation of cell adhesion and transendothelial migration. Analyses of gene and protein expression of target genes revealed that miRNA could affect mRNA levels of certain genes, such as WASP1 and consequently the level of the protein, but also only decrease the translation and the protein quantity without affecting level of mRNA, as observed for BIRC2. In conclusion, these data provide an insight into new molecular mechanisms by which plasma flavanol metabolites at physiologically relevant concentrations may preserve vascular endothelium integrity

Talkmine, a workflow for the prediction of the interactions between secretome and surfaceome in the dialogue between cellular types

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Talkmine, a workflow for the prediction of the interactions between secretome and surfaceome in the dialogue between cellular types

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Cocoa flavanol metabolites modulate signaling pathways and expression of genes involved in monocyte adhesion and transendothelial migration

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Comparative transcriptome analysis of goat (Capra hircus) adipose tissue reveals physiological regulation of body reserve recovery after the peak of lactation

International audienceLe tissu adipeux est l'organe de stockage d'énergie fournissant de l'énergie à d'autres tissus, y compris la glande mammaire, qui soutient la réalisation des cycles de lactation successifs. Notre objectif était d'étudier la capacité des chèvres à reconstituer leurs réserves de graisse corporelle en comparant les activités enzymatiques lipogéniques et par des données transcriptomiques d'ARN-Seq à deux stades physiologiques différents, en milieu et en post-lactation. Les principales activités enzymatiques lipogéniques étaient plus élevées dans le tissu adipeux épiploïque de chèvre pendant la mi-lactation (74 jours dans le lait) que pendant la période post-lactation (300 jours après l'accouchement). L'analyse du séquençage de l'ARN a révélé 19 271 gènes exprimés dans le tissu adipeux omental. La comparaison entre l'analyse du transcriptome adipeux de chèvres en milieu et post-lactation a mis en évidence 252 gènes différentiellement exprimés (p adj< 0,05) entre ces deux stades physiologiques. L'expression différentielle de 11 gènes a été confirmée par RT-qPCR. L'analyse génomique fonctionnelle a révélé que 31 % étaient impliqués dans des processus métaboliques dont 38 % dans le métabolisme des lipides. La plupart des gènes impliqués dans la synthèse des lipides et ceux dans le transport et le stockage des lipides étaient régulés à la hausse dans le tissu adipeux des chèvres en milieu de lactation par rapport à celles en post-lactation. De plus, la plasticité du tissu adipeux a été soulignée par des gènes impliqués dans la signalisation cellulaire et l'intégrité des tissus. Les analyses du réseau ont également mis en évidence trois régulateurs clés du métabolisme des lipides (LEP, APOE et HNF4A) et un gène cible clé (VCAM1). Les plus grandes activités enzymatiques lipogéniques avec la régulation à la hausse des gènes impliqués dans le métabolisme des lipides ont mis en évidence une récupération plus élevée des réserves lipidiques après le pic de lactation que 4 mois après la lactation

Molecular regulation of muscle mass in developing Blonde d’Aquitaine foetuses compared to Charolais

The Blonde d'Aquitaine (BA) is a French cattle breed with enhanced muscularity, partly attributable to a MSTN mutation. The BA m. Semitendinosus has a faster muscle fibre isoform phenotype comprising a higher proportion of fast type IIX fibres compared to age-matched Charolais (CH). To better understand the molecular network of modifications in BA compared to CH muscle, we assayed the transcriptomes of the m. Semitendinosus at 110, 180, 210 and 260 days postconception (dpc). We used a combination of differential expression (DE) and regulatory impact factors (RIF) to compare and contrast muscle gene expression between the breeds. Prominently developmentally regulated genes in both breeds reflected the replacement of embryonic myosin isoforms (MYL4, MYH3) with adult isoforms (MYH1) and the upregulation of mitochondrial metabolism (CKMT2, AGXT2L1) in preparation for birth. However, the transition to a fast, glycolytic muscle phenotype in the MSTN mutant BA is detectable through downregulation of various slow twitch subunits (TNNC1, MYH7, TPM3, CSRP3) beyond 210 dpc, and a small but consistent genome-wide reduction in mRNA encoding the mitoproteome. Across the breeds, NRIP2 is the regulatory gene possessing a network change most similar to that of MSTN

Azgp1 knockout changes mammary gland, adipose tissue and liver gene expression in lactating mice

Session 4: Nutrition to improve milk and meat qualityNational audienc