The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum-fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype

Le système relaxine-3/RXFP3 dans la régulation de la prise alimentaire : effet de la diète, du stress et du facteur sexe

L’hyperphagie et l’obésité sont devenues des problèmes majeurs de notre société et touchent de manière différente les hommes et les femmes. Dès lors, il apparaît nécessaire de rechercher les bases physiologiques de ces troubles chez des modèles animaux, comme les rats développant l’hyperphagie induite par le stress et l’obésité induite par la diète (DIO). Dans ces modèles, l’étude du neuropeptide orexigène relaxine-3 semble être une piste prometteuse du fait de son implication dans la régulation du stress et de la prise alimentaire. Dans un premier temps, nous avons étudié ce neuropeptide chez un modèle animal de rat DIO. Ces rats sont hyperphagiques et défendent leur gain de poids corporel contre la restriction calorique. Nos résultats montrent une expression plus élevée de la relaxine-3 chez les rats DIO lorsqu’ils ont accès à la nourriture à volonté et une expression augmentée de son récepteur RXFP3 induite par la réalimentation suivant le jeûne, suggérant que la relaxine-3 serait impliquée dans le maintien du gain de poids corporel chez le phénotype DIO. Dans une deuxième étude, des rats mâles et femelles étaient soumis à un stress et une restriction alimentaire chronique. Nous avons observé que seules les femelles connaissaient des épisodes d’hyperphagie associés à un gain de poids corporel et une augmentation de l’expression de relaxine-3 qui pourrait être à la base de ce comportement sexuellement spécifique. Dans une troisième étude, par l’injection de relaxine-3 dans le cerveau des rats mâles et femelles, nous avons montré que ce neuropeptide avait un effet orexigène plus élevé chez les femelles que chez les mâles. Nous avons également observé une stimulation plus importante de l’axe corticotrope chez les mâles qui pourrait atténuer l’effet orexigène de la relaxine-3 tandis que, chez les femelles, la stimulation de l’expression de corticolibérine dans le noyau du lit de la strie terminale pourrait renforcer la motivation liée à la recherche de nourriture. En résumé, nos travaux démontrent le rôle du système relaxine-3/RXFP3 dans l’hyperphagie et le gain de poids corporel et montrent son rôle sexuellement spécifique dans la régulation de la prise alimentaire et de la réponse au stress.Hyperphagia and obesity are major problems in our society that affect differentially men and women. Therefore, it is necessary to seek the physiological basis of these health problems using animal models such as stress-induced hyperphagia and diet-induced obesity (DIO) in rats, taking into account diet, stress and sex factors. Investigating the role of the orexigenic neuropeptide relaxin-3 appears to be promising because of its involvement in the regulation of stress and food intake. First, we studied the role of relaxin–3 system in DIO rat model. These rats are hyperphagic and defend their elevated body weight against caloric restriction. The results of this study showed higher expression of relaxin-3 in the DIO rats in free feeding conditions, and, in addition, refeeding after food deprivation led to increased expression of the cognate receptor of relaxin-3 RXFP3 in DIO rats suggesting that relaxin-3 is involved in the defense of elevated body weight in the DIO phenotype. In the second study, hyperphagia was developed in female but not male rats submitted to repeated episodes of food restriction and stress. We observed that female hyperphagic rats showed increased expression of relaxin-3 which could be a cause of this sexually specific behavior. In the third study, by the central injection of relaxin-3 in male and female rats, we showed that female rats were more sensitive to lower doses of relaxin-3 and demonstrated higher increase in food intake compared to male rats. We also observed a greater stimulation of the hypothalamic pituitary adrenal (HPA) axis in male rats that may limit the orexigenic effect of relaxin-3. Conversely, in female rats, stimulation of corticotropin-releasing factor expression in the bed nucleus of the stria terminalis may enhance feeding behavior. In summary, our work demonstrates the role of relaxin-3/RXFP3 system in hyperphagia and body weight gain and shows its sex-specific effects in food intake regulation and stress response

Le projet Ifremmont : Création d’une base de données et d’un centre de ressources international en médecine de montagne

Mémoire de Master Pro Information et Communication, "Mention Sciences de l\u27information" de l\u27Université Montpellier III Paul Valéry, à Béziers. Ce mémoire détaille la mise en place technique et fonctionnelle de Docmmont, base de données du Département de médecine et de traumatologie de montagne (DMTM) de l\u27hôpital de Chamonix

The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum-fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype

Le projet Ifremmont : Création d'une base de données et d'un centre de ressources international en médecine de montagne

Ce stage a été effectué au DMTM de L'hôpital de Chamonix cette association porte également le nom du projet Ifremmont. Ifremont et DMTM sont la même structure. Ce mémoire n'a pas été soutenu mais le Master a été validé avec mention bien.Under the project Ifremmont, DMTM wished to establish a resource centre named Docmmont. The aim is to publicize studies of this research group in mountain medicine and to facilitate access to documents. The database Docmmont was created with the software “Alexandrie” to be available on Internet. It contains documents of three associations: the DMTM, Arpe and the Cerna.Dans le cadre du projet Ifremmont, le DMTM a souhaité mettre en place un centre de documentation nommé Docmmont. L'objectif est de faire connaître les études de ce groupe de recherche en médecine de montagne mais aussi de faciliter l'accès aux documents. La base de données Docmmont a été créée avec le logiciel « Alexandrie » afin d'être diffusée sur internet. Elle contient les documents de trois associations : le DMTM, l'Arpe et le Cerna

The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum-fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype

Involvement of orexin in the sex-specific effect of relaxin-3 on food intake in rats

Involvement of orexin in the sex-specific effect of relaxin-3 on food intake in rats. 24. Annual Meeting of the International Behavioral Neuroscience Society (IBNS