Modulation of inter-organ signalling in obese mice by spontaneous physical activity during mammary cancer development

International audienceAccumulative evidence links breast cancer development to excess weight and obesity. During obesity, dysregulations of adipose tissue induce an increase in pro-inflammatory adipokine secretions, such as leptin and oestrogen secretions. Furthermore, a raise in oxidative stress, along with a decrease in antioxidant capacity, induces and maintains chronic inflammation, which creates a permissive environment for cancer development. Physical activity is recommended as a non-pharmacological therapy in both obese and cancer situations. Physical activity is associated with a moderation of acute inflammation, higher antioxidant defences and adipokine regulation, linked to a decrease of tumour-cell proliferation. However, the biological mechanisms underlying the relationship between oxidative stress, low-grade inflammation, carcinogenesis, obesity and physical activity are poorly understood. Our study is based on old, ovariectomised mice (C57BL/6J mice, 33 weeks old), fed with a high fat diet which increases adipose tissue favouring overweight and obesity, and housed in either an enriched environment, promoting physical activity and social interactions, or a standard environment constituting close to sedentary conditions. Our model of mammary carcinogenesis allowed for the exploration of tissue secretions and signalling pathway activation as well as the oxidative status in tumours to clarify the mechanisms involved in a multiple factorial analysis of the data set. The multiple factorial analysis demonstrated that the most important variables linked to moderate, spontaneous physical activity were the increase in growth factor (epithelial growth factor (EGF), hepatocyte growth factor (HGF)) and the activation of the signalling pathways (STAT3, c-jun n-terminal kinases (JNK), EKR1/2, nuclear factor-kappa B (NF-kappa B)) in the gastrocnemius (G). In inguinal adipose tissue, the NF-kappa B inflammation pathway was activated, increasing the IL-6 content. The adiponectin plasma (P) level increased and presented an inverse correlation with tumour oxidative status. Altogether, these results demonstrated that spontaneous physical activity in obesity conditions could slow down tumour growth through crosstalk between muscle, adipose tissue and tumour. A spontaneous moderate physical activity was able to modify the inter-organ exchange in a paracrine manner. The different tissues changed their signalling pathways and adipokine/cytokine secretions, such as adiponectin and leptin, resulting in a decrease in anti-oxidative response and inflammation in the tumour environment. This model showed that moderate, spontaneous physical activity suppresses tumour growth via a dialogue between the organs clos

L’activité physique spontanée en condition d’obésité module les signaux hormonaux tissulaires conduisant à une moindre croissance tumorale

Laboratoire de Biochimie, Biologie moléculaire et Nutrition,Equipe ECREINLes dérégulations du tissu adipeux en obésité maintiennent une inflammation chronique favorisant un microenvironnement pro-carcinogène. L’activité physique (AP), un facteur de prévention de l’obésité et des cancers, favorise la réponse anti-oxydante et la sécrétion d’adipokines anti-inflammatoires mais les mécanismes, dans le cancer mammaire, restent mal connus. Le but est de caractériser l’impact de l’AP spontanée sur la croissance tumorale dans un modèle de carcinogenèse mammaire murin en situation d’obésité.Des souris C57BL/6 âgées (n=10/groupe), ovariectomisées, nourries avec un régime hyper-lipidique, sont hébergées en environnement standard (ES) ou en environnement enrichi (EE). Après 4 semaines, des cellules tumorales syngéniques EO771 sont implantées par fat-pad avant d’explorer au sacrifice les cytokines et voies de signalisation dans la tumeur, le tissu adipeux inguinal (TAI), le gastrocnémien et plasma.L’analyse factorielle multiple des paramètres montre que l’AP modérée induit au niveau tumoral une diminution de l’activation de NFκB s’accompagnant d’une baisse des métabolites et enzymes antioxydants. Dans le gastrocnémien, une augmentation de l’activation de STAT3, ERK1/2 et NFκB est observée. La quantité de leptine, du gastrocnémien fortement diminué, corrèle positivement avec la quantité de leptine intra-tumorale, alors que dans le TAI, les taux tissulaires de leptine et d’adiponectine ne sont pas modifié malgré une augmentation de la masse du TAI et du taux circulant d’adiponectine.Ces résultats montrent que l’AP spontanée en condition d’obésité ralentie la croissance tumorale en réduisant l’inflammation et le stress oxydatif du microenviroronnement via une moindre activation des voies de signalisation tumoral. Cet effet semble reposé sur une modulation des signaux hormonaux au travers des autres tissus

Omics data reveal putative regulators of einkorn grain protein composition under sulfur deficiency

International audienceUnderstanding the molecular mechanisms controlling the accumulation of grain storage proteins in response to nitrogen (N) and sulfur (S) nutrition is essential to improve cereal grain nutritional and functional properties. Here, we studied the grain transcriptome and metabolome responses to postanthesis N and S supply for the diploid wheat einkorn (Triticum monococcum). During grain filling, 848 transcripts and 24 metabolites were differentially accumulated in response to N and S availability. The accumulation of total free amino acids per grain and the expression levels of 241 genes showed significant modifications during most of the grain filling period and were upregulated in response to S deficiency. Among them, 24 transcripts strongly responded to S deficiency and were identified in coexpression network analyses as potential coordinators of the grain response to N and S supply. Sulfate transporters and genes involved in sulfate and Met metabolism were upregulated, suggesting regulation of the pool of free amino acids and of the grain N-to-S ratio. Several genes highlighted in this study might limit the impact of S deficiency on the accumulation of grain storage proteins.Sulfur deficiency in einkorn grain leads to upregulation of genes acting in sulfur transport and metabolism that may coordinate the pool of free amino acids necessary for storage protein synthesis

PanGeneHome : A Web Interface to Analyze Microbial Pangenomes

International audiencePanGeneHome is a web server dedicated to the analysis of available microbial pangenomes. For any prokaryotic taxon with at least three sequenced genomes, PanGeneHome provides (i) conservation level of genes, (ii) pangenome and core-genome curves, estimated pangenome size and other metrics, (iii) dendrograms based on gene content and average amino acid identity (AAI) for these genomes, and (iv) functional categories and metabolic pathways represented in the core, accessory and unique gene pools of the selected taxon. In addition, the results for these different analyses can be compared for any set of taxa. With the availability of 615 taxa, covering 182 species and 49 orders, PanGeneHome provides an easy way to get a glimpse on the pangenome of a microbial group of interest. The server and its documentation are available at http://pangenehome.lmge.uca.fr