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9 pages; International audience; Parasitic organisms have to cope with the defences deployed by their hosts and this can be achieved adopting immune evasion strategies or optimal life history traits according to the prevailing pattern of immune-mediated mortality. Parasites often encounter variable immune environments both within and between hosts, promoting the evolution of plastic strategies instead of fixed responses. Here, we explored the plasticity and micro-evolutionary responses of immunomodulatory mechanisms and life history traits to the immune environment provided by the host, using the parasitic nematode Heligmosomoides polygyrus. To test if the parasite responds plastically to the immune environment, we stimulated the systemic inflammatory response of mice and we assessed i) the expression of two genes with candidate immunomodulatory functions (Hp-Tgh2 and Hp-CPI); ii) changes in the number of eggs shed in the faeces. To test if the immune environment induces a micro-evolutionary response in the parasite, we maintained the nematode in mice whose inflammatory response was up- or down-regulated during four generations. We found that H. polygyrus plastically responded to a sudden rise of pro-inflammatory cytokines, up-regulating the expression of two candidate genes involved in the process of immune modulation, and enhancing egg output. At the micro-evolutionary level, parasites maintained in hosts experiencing different levels of inflammation did not have differential expression of Hp-Tgh2 and Hp-CPI genes when infecting unmanipulated, control, mice. However, parasites maintained in mice with an up-regulated inflammation shed more eggs compared to the control line. Overall, our study shows that H. polygyrus can plastically adjust the expression of immunomodulatory genes and life history traits, and responds to selection exerted by the host immune system.

International audience; The endocannabinoid system is composed of G-protein receptors named Cannabinoid type 1-Receptor (CB1-R) and Cannabinoid type 2-Receptor (CB2-R), their endogen ligands (anandamide [AEA], and 2-acylglycerol [2-AG]) and the enzymes responsible for their synthesis and degradation. Although CB1-R and CB2-R were first described in the central neuronal system, they are present in several other tissues, where they are involved in metabolism, growth, and inflammation. After the withdrawal of rimonabant, a specific CB1-R inverse agonist used in the treatment of type 2 diabetes and obesity, because of neuropsychiatric side effects; targeting endocannabinoid system still remains a promising approach in the treatment of many pathophysiological process like metabolic syndrome, cancer, and neuronal affections [1]. Indeed, many arguments in animal models and Human raise the role of endocannabinoids in the onset of insulin resistance and obesity.The aim of this article is to present an update on past and recent knowledge on endocannabinoids and metabolism, and future perspectives for the treatment of metabolic disorders, including dyslipidemia associated with the metabolic syndrome.; RésuméLe système endocannabinoïde (SEC) est composé de récepteurs couplés aux protéines G : Cannabinoid type 1-receptor (CB1-R) et Cannabinoid type 2-receptor (CB2-R), de leurs ligands endogènes (anandamide [AEA], et 2-acylglycérol [2-AG]), et des enzymes responsables de leur synthèse et de leur dégradation. Bien que les récepteurs CB1-R et CB2-R furent initialement décrits au niveau du système nerveux central, ils sont présents dans de nombreux tissus périphériques, où ils sont impliqués dans le métabolisme, la croissance, et l’inflammation. Après le retrait commercial du rimonabant, pour des effets secondaires psychiatriques, un agoniste inverse du récepteur CB1 (CB1-R), destiné au traitement du diabète de type 2 et de l’obésité, le SEC reste cependant une cible intéressante pour le traitement de nombreuses affections, comme le syndrome métabolique, le cancer, et les maladies neurodégénératives [1]. En effet, de nombreuses études conduites chez l’animal et l’Homme soulignent le rôle des endocannabinoïdes dans le développement de l’insulino-résistance et de l’obésité.Cet article vise à faire le point sur les connaissances passées et récentes sur les effets des endocannabinoïdes dans le métabolisme énergétique glucido-lipidique, et les futures perspectives pour la prise en charge des désordres métaboliques, notamment les dyslipidémies associées au syndrome métabolique.

IF 4.066; International audience

International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but only when the diet contains lipids. This drop is significant 1 h after a lipid supply and associates with ubiquitination of CD36. Using CHO cells expressing CD36, it is shown that the digestion products LCFA and diglycerides trigger CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevents the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 is shown to be required for lipid activation of ERK1/2, which associates with an increase of the key chylomicron synthesis proteins, apolipoprotein B48 and microsomal triglyceride transfer protein. Therefore, intestinal CD36, possibly through ERK1/2-mediated signaling, is involved in the adaptation of enterocyte metabolism to the postprandial lipid challenge by promoting the production of large triglyceride-rich lipoproteins that are rapidly cleared in the blood. This suggests that CD36 may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks.

International audience; Cyclopropane fatty acid (CFA) synthesis was investigated in Oenococcus oeni. The data obtained demonstrated that acid-grown cells or cells harvested in the stationary growth phase showed changes in fatty acid composition similar to those of ethanol-grown cells. An increase of the CFA content and a decrease of the oleic acid content were observed. The biosynthesis of CFAs from unsaturated fatty acid phospholipids is catalysed by CFA synthases. Quantitative real-time-PCR experiments were performed on the cfa gene of O. oeni, which encodes a putative CFA synthase. The level of cfa transcripts increased when cells were harvested in stationary phase and when cells were grown in the presence of ethanol or at low pH, suggesting transcriptional regulation of the cfa gene under different stress conditions. In contrast to Escherichia coli, only one functional promoter was identified upstream of the cfa gene of O. oeni. The function of the cfa gene was confirmed by complementation of a cfa-deficient E. coli strain. Nevertheless, the complementation remained partial because the conversion percentage of unsaturated fatty acids into CFA of the complemented strain was much lower than that of the wild-type strain. Moreover, a prevalence of cycC19 : 0 was observed in the membrane of the complemented strain. This could be due to a specific affinity of the CFA synthase from O. oeni. In spite of this partial complementation, the complemented strain of E. coli totally recovered its viability after ethanol shock (10 %, v/v) whereas its viability was only partly recovered after an acid shock at pH 3.0.