Miniature pig as a model for translational therapy – vagal stimulation and metabolic syndrome

L’innovation thérapeutique dans la lutte contre l’obésité morbide chez l’homme se heurte aux limites du modèle rongeur et justifie l’utilisation du porc miniature rendu obèse par une alimentation pléthorique. Ce dernier ne développe aucune des comorbidités décrites chez l’homme : diabète, troubles cardiovasculaires et syndrome métabolique, mais il présente toutes les altérations nerveuses centrale et périphérique identifiées chez le patient. C’est pourquoi, il représente un modèle particulièrement pertinent pour évaluer les conséquences de la stimulation vagale chronique visant à rétablir le trafic nerveux entre le tube digestif et le cerveau. Cette pratique réduit durablement, chez le porc, l’ingestion et accroit le métabolisme intermédiaire conduisant à une réduction de la prise de poids. Elle rétablit la sensibilité à l’insuline au niveau de l’organisme entier et des organes clés de l’homéostasie glucidique. Ces effets résultent d’une modulation directe et indirecte des réseaux limbiques via la normalisation du trafic dopaminergique mésolimbique.Therapeutic innovation against morbid obesity requires alternate animal models such as the diet induced obese miniature pig. While it does not develop the panel of diseases associated with obesity such as diabetes, atherosclerosis and metabolic syndrome, central and peripheral nervous signals are altered similar to humans. These peculiarities make the porcine model of significant interest to study the consequences of chronic vagal stimulation (VNS) on the recovery of the nervous traffic between the gut and the brain. VNS reduced food intake and increased resting energy expenditure resulting in a reduction of weight gain. Insulin sensitivity was recovered as a consequence of improved glucose uptake of key organs for glucose homeostasis. These effects were the consequence of a direct and indirect modulation of limbic networks via a further improvement of mesolimbic dopamine trafficking

Central activation after chronic vagus nerve stimulation in pigs : contribution of functional imaging

Chronic vagus nerve stimulation (VNS), used to treat refractory epilepsy, has the potential to alter food intake in animals and humans. The aim of our study was to evaluate the impact of VNS on the feeding behaviour of pigs used as a human model, and to investigate the origin of its potential effects. Food intake was significantly decreased after five weeks of chronic VNS. This reduction was not due to stimulation of the vagus efferents as neither gastric compliance nor gastric emptying was altered. VNS triggered a reorganisation of brain activation, probably via subcortical structures involved in the reward mechanism. The activation of the olfactory bulb during VNS is probably one of the mechanisms responsible for the drastic changes in food preference in favour of lipids.La stimulation vagale chronique (VNS), une thérapeutique de l'épilepsie pharmacorésistante, serait capable chez l'animal et chez l'homme de modifier le comportement alimentaire. Le but de notre étude était de préciser l'impact de la VNS sur le comportement alimentaire du porc pris comme modèle de l'homme et d'étudier l'origine de ses effets potentiels. La VNS conduit au bout de cinq semaines à une réduction de la quantité d'aliment ingéré. Cette réduction n'est pas la conséquence de la stimulation des efférences vagales, la compliance ou l'évacuation de l'estomac, n'étant pas modifiée. Par contre, la VNS provoque une réorganisation de l'activation cérébrale mettant vraisemblablement en jeu les structures sous-corticales impliquées dans le processus de récompense. L'activation du bulbe olfactif au cours de la VNS est probablement l'un des éléments à l'origine des modifications drastiques des préférences alimentaires en faveur des lipides

Vagus nerve stimulation: State of the art of stimulation and recording strategies to address autonomic function neuromodulation

International audienceObjective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans

Mesure de l'évacuation de l'estomac par gamma scintigraphie

National audienc

Vagally Mediated Gut-Brain Relationships in Appetite Control-Insights from Porcine Studies

Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Furthermore, its large size combined with the capacity to become obese while overeating a western diet makes it a pivotal addition to existing murine models, especially for translational studies relating to obesity. How gastric, proximal intestinal, and portal information relating to meal arrival and transit are encoded by vagal afferents and their further processing by primary and secondary brain projections are reviewed. Their peripheral and central plasticities in the context of obesity are emphasized. We also present recent insights derived from chronic stimulation of the abdominal vagi with specific reference to the modulation of mesolimbic structures and their role in the restoration of insulin sensitivity in the obese miniature pig model

1.3. Neurosciences et comportement alimentaire – Le plaisir de manger

Manger constitue une expérience agréable et enrichissante. Il n’est donc pas surprenant que les centres du cerveau impliqués dans le plaisir et la récompense soient activés lorsque nous mangeons. Les mécanismes neurobiologiques fondamentaux propres à la récompense alimentaire sont d’une importance considérable pour comprendre comment est régulé le poids corporel. La prise d’aliments est motivée non seulement par la nécessité de rétablir l’homéostasie* énergétique mais aussi par le plaisir att..

L'axe tube digestif-cerveau : avancées récentes obtenues sur un modèle d'obésité chez le porc

National audienceThe pig, which shares several similarities with humans, is increasingly used for biomedical research, particularly in nutrition and neurosciences. Recent studies in minipigs have shown that a deleterious nutritional environment (e.g. a high-fat and high-sugar diet) induces obesity which, as in humans, is associated with increased adiposity, insulin resistance, modified eating behaviour, and altered gastric function and intestinal sensitivity. These changes are accompanied by differences in the activation matrices and metabolic activity of several brain areas. Using this animal model, we have revisited the concept of dual hedonic and homeostatic control of food intake. We have thus developed a minimally invasive and potentially reversible surgical approach to the control of food intake, as an alternative to bariatric surgery, based on chronic vagal stimulation at the abdominal level.Par sa proximité avec l’homme, le porc et plus particulièrement le porc miniature est devenu un modèle privilégié en nutrition et neurosciences. Chez ce dernier, un environnement nutritionnel délétère permet d’induire une obésité accompagnée, tout comme chez l’homme, d’une augmentation dramatique de l’adiposité, d’une résistance à l’insuline, d’un bouleversement des comportements alimentaires, de modifications de la fonction gastrique et d’une altération de la sensibilité intestinale. Ces phénomènes sont associés à des changements d’activation et de métabolisme de diverses zones cérébrales. Ce même modèle animal a permis de reconsidérer le concept d’une double valence hédonique et homéostatique contrôlant la prise alimentaire. Sur cette base, nous avons développé une stratégie minimalement invasive et réversible de contrôle de la prise alimentaire utilisant la stimulation chronique du nerf vague qui est susceptible d’offrir une alternative à la chirurgie bariatrique

Animal et douleur

Ouvrage collectif d'enseignement. Programme européen Partie 2 : Éthique de l'animalNational audienc

Brain imaging during feeding behaviour

Session : Nutrition, alimentation, gustationNational audienceWithin the last decade, fMRI data in humans had point out the critical role of the hedonic component in the control of food intake. Taken into account the massive knowledge existing on the importance of the hypothalamus on virtually the same target i.e. weight control, it has been postulated that food intake was under the control of two independent networks: the hedonic and the homeostatic networks. Recent data obtained using functional imaging in humans and in animals models suggests that the situation is more complex. First non painful gastric distension mimicking that occurring immediately after the meal is not only able to activate nuclei directly associated to ascendant projections from the dorsal vagal complex but also limbic areas including prefrontal and orbito-frontal cortices. Second, we recently demonstrated that both duodenal and portal glucose infusions activated the dorsolateral prefrontal cortex and the primary somatosensory cortex. Third, Wang team has demonstrated in some obese individuals a decreased activity of the prefrontal cortex. We have showed using a large animal model, that this decreased activity is an acquire feature of obesity and not a pre-existent item. All these data militates in favour of a single network that process homeostatic and hedonic data

Mesure de l'évacuation de l'estomac par gamma scintigraphie

National audienc