LE GALL Maud (Equipe BADO)
Transcription
LE GALL Maud (Equipe BADO)
ED BIO SORBONNE PARIS CITE Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2016-2017 Renseignements relatifs à l’Unité de Recherche : Label et intitulé : Centre de Recherche sur l’Inflammation, UMRS 1149 Nom et prénom du Directeur : MONTEIRO Renato Téléphone : 01 57 27 77 55 Télécopie : 01 57 27 74 71 Courriel: [email protected] Renseignements relatifs à l’Equipe : Nom de l’Equipe d’Accueil : Bariatric Surgery, Alimentary Disease, and Obesity Nom et prénom du responsable : André BADO Qualité du responsable : DR2 Inserm Téléphone : 01 57 27 74 60 Télécopie : 01 57 27 74 71 Courriel : [email protected] Renseignements relatifs au sujet de thèse : Nom et prénom du Directeur de thèse (HDR) : LE GALL Maude Qualité : CR1 Inserm Téléphone : 01 57 27 74 59 Télécopie : 01 57 27 74 71 Courriel : [email protected] Titre du sujet proposé : (En français) Absorption des nutriments après chirurgie bariatrique : mécanismes de l’adaptation intestinale et métabolique (En anglais) Bariatric surgery procedures and nutrient absorption: mechanisms of intestinal and metabolic adaptations Département (cocher le département correspondant au sujet de thèse qui n’est pas obligatoirement le vôtre) : Biologie Cellulaire et moléculaire, Physiologie et Physiopathologie Immunologie Développement Génétique Neurobiologie et Vieillissement Infectiologie, Microbiologie Summary (5 lines maximum) : Today, the most effective treatment option for morbid obesity that leads to a rapid and sustained loss in body weight and resolution of associated diabetes is bariatric surgery. All bariatric surgery remodeled the gastro-intestinal tract. The objectives of the thesis are to decipher the molecular and cellular mechanisms of intestinal adaptation after bariatric surgery and their contribution to maintained weight loss and diabetes resolution using rat models of surgery. Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2016-2017 (L’ensemble de cette fiche ne doit pas dépasser 1 page) Nom, prénom du directeur de l'unité de recherche : MONTEIRO Renato Numéro de l'unité de recherche (et établissement de rattachement) : UMRS1149 Nom, prénom du responsable de l'équipe d'accueil (EAD) : André BADO Nom, prénom du directeur de thèse : Maude LE GALL Titre du sujet de thèse proposé(en anglais) : Bariatric surgery procedures and nutrient absorption : mechanisms of intestinal and metabolic adaptations 5 mots clés : obésité, transporteurs intestinaux des nutriments, plasticité entéro-endocrine et neuronale (key words): obesity, intestinal transporters of nutrients, entero-endocrine and neuronal plasticity Candidat pressenti : OUI NON Contenu scientifique du programme de la thèse (en anglais) The overall rise in obesity is to a large degree responsible for the increased incidence of diseases like type 2 diabetes mellitus. Today, the most effective treatment option that leads to a rapid and sustained loss in body weight is bariatric surgery, such as Roux-en-Y gastric bypass (RYGB). Vertical sleeve gastrectomy (VSG) is another frequently used bariatric procedure. Despite the very different surgical approach, RYGB and VSG are associated with similar hormonal changes. A third bariatric surgery procedure is the so-called mini-gastric bypass (MGB) which has been introduced approx. 20 years ago. Because it is technically less challenging, this technique is used more and more often, in particular in non-academic surgical centers. Surprisingly little research has been performed to study the underlying mechanisms that lead to body weight loss and diabetes remission after MGB. Since the last 3 years, we have successfully developed rat models of bariatric surgery (Theses of K Arapis (digestive Surgeon) and JB Cavin (scientist)) to decipher the molecular mechanisms underlying their benefic effects. We have explored sugar handling after RYGB and VSG but not MGB yet. The handling of lipids and protein by the remodeled intestine is still to be explored. Currently, PhD Student L Ribeiro (digestive Surgeon) is exploring the remodeling of enteric nervous system (ENS) after surgery and its contribution to maintained weight loss. Thesis project aims at clarifying the underlying mechanisms that lead to weight loss after MGB, and to compare these effects directly to the RYGB and VSG procedures. The PhD candidate will study protein and lipid absorption by the remodeled intestine after the different surgeries. The PhD candidate will also continue to explore the mechanisms of sugar handling after bariatric surgeries, in particular after MGB. In part of the experiments, he will specifically examine contribution of the small intestinal mucosal hypertrophy to the effectiveness of RYGB and MGB in relation to nutrient absorption, intestinal endocrine functions, feeding behavior and remodeling of the ENS. The experiments will be performed using rat models of RYGB, VSG and MGB that are established in our laboratories. Indiquez les cinq meilleures publications récentes de l’équipe : Michau, A. *, Guillemain, G. *,…, Le Gall, M. (2013). Mutations in SLC2A2 gene reveal hGLUT2 function in pancreatic β cell development. J. Biol. Chem. 288, 31080–31092. Tavernier, A., Cavin, J.-B., Le Gall, M., …, Bado, A. (2014). Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice. FASEB J. 28, 4100–4110. Le Beyec, J., ...., Le Gall, M., Bado, A. (2014). Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells. Int. J. Obes. 38, 1357–1364. Arapis, K.*, Cavin, J.B.*, Gillard, L.,…, Le Gall, M., Bado, A. (2015). Remodeling of the Residual Gastric Mucosa after Roux-En-Y Gastric Bypass or Vertical Sleeve Gastrectomy in Diet-Induced Obese Rats. PLoS ONE 10, e0121414. Cavin, J.-B., …., Bado, A., Le Gall, M. (2016). Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose Following Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy. Gastroenterology 150(2):454-464
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