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

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

Animal et douleur

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

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..

Vagally mediated effects of motilin and motilides in the pig

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The ileocolonic sphincter

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Methods for recording flow

*INRA UMR Veau et Porc Rennes (FRA) Diffusion du document : INRA UMR Veau et Porc Rennes (FRA)International audienc

AniMate - An open source software for absolute PET quantification

AniMate - An open source software for absolute PET quantification. Annual congress of the european association of nuclear medicin