57 research outputs found
Le modĂšle porcin naturel de retard de croissance pour lâĂ©tude de la programmation mĂ©tabolique et lâobĂ©sitĂ©
Le retard de croissance intra-utérin (RCIU) demeure un problÚme non résolu en
médicine périnatale. Le RCIU est reconnu comme une des causes principales de
morbiditĂ© pĂ©rinatale et rĂ©sulte, entre autres, dâun mauvais environnement
maternel et dâune insufïŹsance placentaire. Lâenvironnement maternel inadĂ©quat
met en danger non seulement la vie du nouveau né mais a des répercussions à long
terme sur la vie du futur adulte. Des études épidémiologiques ont en effet
démontré que le RCIU est associé à un risque élevé de développement de
pathologies tardives tels que lâhypertension, le diabĂšte de type 2 et lâobĂ©sitĂ©.
Cette association a donné lieu au concept bien connu de programmation
métabolique développé par BARKER en 1994. De maniÚre intéressante, les modÚles
animaux mimant la situation chez lâhomme sont dâexcellents outils pour
comprendre les mécanismes génétiques, moléculaires et cellulaires sous jacents.
Historiquement les petits rongeurs ont Ă©tĂ© les modĂšles prĂ©dominants dâĂ©tude de
la programmation fĆtale et plusieurs techniques ont Ă©tĂ© dĂ©veloppĂ©es sur cette
espÚce pour induire expérimentalement des animaux RCIU. Récemment, le modÚle
porcin naturel de retard de croissance a été reconnu comme intéressant pour
lâĂ©tude de la programmation mĂ©tabolique et lâobĂ©sitĂ©. En effet, comme chez le
RCIU humain, le porc RCIU prĂ©sente les mĂȘme signes de croissance
adaptatrice/compensatrice entrainant une augmentation de lâadipositĂ© au cours de
la vie adulte. De plus, les processus de croissance et de développement des
organes du porc sont semblables Ă ceux dĂ©crits chez lâHomme. En utilisant ce
modÚle, nous avons montré que quelques jours aprÚs la naissance les porcs RCIU
prĂ©sentent une altĂ©ration de la distribution de lâexpression du rĂ©cepteur de la
leptine au niveau des noyaux hypothalamiques. Nous avons observé une altération
de la structure du tissu adipeux chez le porc RCIU avec une grande densité de
petites cellules adipocytaires. AprĂšs le sevrage, les animaux accusent une
croissance postnatale rapide entrainant une augmentation de lâadipositĂ© Ă un Ăąge
plus avancé (J 165). Le traitement postnatal par la leptine inverse
partiellement le phĂ©notype de lâIUGR en corrigeant la vitesse de croissance, la
composition corporelle et rétablit le poids et la structure de certains organes
impliqués dans la régulation métabolique. Ces résultats pourraient contribuer au
dĂ©veloppement dâune nouvelle thĂ©rapie pour la lutte contre la programmation
mĂ©tabolique et le dĂ©veloppement Ă long terme de lâobĂ©sitĂ©
Vaccination contre les récepteurs aux hormones gonadotropes chez la truite arc-en-ciel : une méthode alternative pour le contrÎle de la puberté ?
National audienc
Delayed sexual maturation through gonadotropin receptor vaccination in the rainbow trout <em>Oncorhynchus mykiss</em>
International audienceIn fish, gonadotropin hormones FSH-GTH1 and LH-GTH2 are less specific for their cognate receptors than in mammals. The respective reproductive functions of fish LH and FSH are thus difficult to establish. We aimed to study the effect of specific antagonists of the two gonadotropin receptors on trout sexual maturation in both sexes by targeting specific regions of LH and FSH receptors, Lhr and Fshr. Filamentous phages displaying Lhr specific or Fshr specific decapeptides from the extracellular hormone binding domain were engineered. Recombinant phages were used as receptor-specific antagonistic vaccines. Male and female trouts were immunized with anti-LHR, anti-FSHR, anti-FSHR + LHR or adjuvant alone, through multiple injections over 8-24 weeks, starting at different stages of sexual maturation. The consequences of immunization on gonadal development were evaluated by determining gonad growth, by histological analysis of testis and ovaries at the end of the vaccination period and by measuring blood plasma sex steroids using radioimmunoassay. We show for the first time in fish that the anti-receptor vaccinations could have specific antagonistic effects on the development of the reproductive functions; while the anti-FSHR affected the sexual maturation of prepubertal males and delayed sperm production, the anti-LHR blocked vitellogenesis in females. In maturing males, the combined anti-FSHR+LHR vaccine inhibited spermatogenesis and affected steroidogenesis. In that case, the effects of the vaccine on spermatogenesis were transient and reversible when immunization was stopped. Such an immunological strategy to specifically and transiently inhibit a receptor provides a promising approach for discovering their specific functions; it could also lead to a new technology for controlling the onset of puberty in aquaculture species
Active immunization against gonadotropin receptors can impair reproductive function in rainbow trout
National audienceThe consequences of immunization against specific regions of gonadotropin receptors were analysed in rainbow trout, on gonadal development and plasma testosterone levels. Males immunized against LHR alone or in combination with FSHR, showed a decrease in mean GSI. related to an inhibition of the spermatogenetic process; females immunized against FSHR or LHR exhibited delayed vitellogenesis. Vaccination against FSHR, and to a less extent against LHR, had a global inhibitory effect on plasma testosterone levels
DOHaD : conséquences à long terme de la pathologie périnatale
The first epidemiological studies showing a link between low birth weight and chronic diseases in adults did not distinguish the origins of low birth weight. A low birth weight may be the result of a premature birth. It can also be caused by an intrauterine growth restriction (IUGR). A child can be both preterm and IUGR. It is clear now that prematurity is an independent risk factor for programming chronic adult diseases. However, unlike adults born IUGR, adults born prematurely do not have an increased risk to develop metabolic syndrome (dyslipidemia or obesity). An increased risk of neurodevelopmental and psychiatric morbidity and hypertension is found after a premature birth. Mechanisms of chronic diseases programming are multiple: they involve both the cause of prematurity and IUGR such as infection / inflammation or placental insufficiency, but also consequences for therapeutic or nutritional strategies needed to support these children. This chapter describes the possible prevention of perinatal programming of noncommunicable diseases.Les premiĂšres Ă©tudes Ă©pidĂ©miologiques qui montraient un lien entre petit poids de naissance et survenue de maladies chroniques de lâadulte ne distinguaient pas les origines du petit poids de naissance. Un petit poids de naissance peut ĂȘtre le fait dâune naissance prĂ©maturĂ©e. Il peut aussi ĂȘtre secondaire Ă un ralentissement de la croissance fĆtale appelĂ© retard de croissance intra-utĂ©rin (RCIU). Un enfant peut Ă la fois ĂȘtre nĂ© prĂ©maturĂ©ment et porteur dâun RCIU. Il apparaĂźt clairement que la grande prĂ©maturitĂ© est un facteur de risque â indĂ©pendant du poids de naissance â de la programmation de maladies chroniques de lâadulte. Cependant, contrairement Ă ceux qui sont nĂ©s avec un retard de croissance intra-utĂ©rin, les adultes qui sont nĂ©s prĂ©maturĂ©ment nâont pas une propension accrue de dĂ©velopper un syndrome mĂ©tabolique (dyslipidĂ©mie ou obĂ©sitĂ©). Un risque accru de morbiditĂ© neurodĂ©veloppementale et psychiatrique et dâhypertension artĂ©rielle a, en revanche, Ă©tĂ© bien dĂ©crit chez les individus nĂ©s prĂ©maturĂ©s. Les mĂ©canismes qui associent prĂ©maturitĂ© et retard de croissance intra-utĂ©rin Ă la survenue plus tardive, au cours de la vie, de pathologies chroniques sont multiples : ils impliquent Ă la fois la cause de la prĂ©maturitĂ© et du retard de croissance intra-utĂ©rin, telles quâune infection/inflammation ou une insuffisance placentaire, mais aussi les consĂ©quences des stratĂ©gies thĂ©rapeutiques ou nutritionnelles nĂ©cessaires Ă la prise en charge de ces enfants. Cette revue dĂ©crit les moyens de prĂ©vention possible de la programmation pĂ©rinatale des maladies chroniques de lâadulte
Active immunization against gonadotropin receptors can impair reproductive function in rainbow trout
National audienceThe consequences of immunization against specific regions of gonadotropin receptors were analysed in rainbow trout, on gonadal development and plasma testosterone levels. Males immunized against LHR alone or in combination with FSHR, showed a decrease in mean GSI. related to an inhibition of the spermatogenetic process; females immunized against FSHR or LHR exhibited delayed vitellogenesis. Vaccination against FSHR, and to a less extent against LHR, had a global inhibitory effect on plasma testosterone levels
Vaccination contre les récepteurs aux hormones gonadotropes chez la truite arc-en-ciel : une méthode alternative pour le contrÎle de la puberté ?
National audienc
Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function
Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10âÎŒmol/l) with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine). Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6âmM), MG induced a significant (P<0.05) increase of insulin secretion. By contrast, in higher glucose concentrations (8.3âmM and 16.7âmM), MG significantly inhibited insulin secretion (P<0.05). In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (P<0.05), while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (P<0.05). Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells
Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function
Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 mol/l) with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine). Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM), MG induced a significant ( < 0.05) increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM), MG significantly inhibited insulin secretion ( < 0.05). In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion ( < 0.05), while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion ( < 0.05). Conclusion. We suggest that MG modulates the secretion activity of betacell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells
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