Plasticité gastrointestinale et conséquences physiologiques : leçons de la chirurgie bariatrique

Aujourd’hui, face à l’épidémie d’obésité, de plus en plus de personnes ont recours à la chirurgie bariatrique, qui permet une perte de poids importante et une amélioration des conditions métaboliques associées à l’obésité. L’adaptation gastro-intestinale après la chirurgie et ses conséquences métaboliques sont cependant peu connues. Nous avons développé des modèles murins de bypass gastriques et de gastrectomie longitudinale (sleeve) et nous avons caractérisé l’adaptation morphologique et fonctionnelle de l’épithélium gastro-intestinal après ces chirurgies afin de comprendre l’origine des améliorations métaboliques. Nous avons montré que l’estomac était remodelé après les deux chirurgies, suggérant une augmentation de la production acide par les cellules pariétales et une altération de la production de gastrine et de ghréline. Après le bypass, l’anse alimentaire était hyperplasique et la consommation intestinale de glucose était augmentée chez le rat et l’homme; après la sleeve, l’absorption de glucose lors du repas était diminuée. De plus, l’augmentation du nombre de cellules entéroendocrines observée après le bypass, et l’augmentation de leur densité après la sleeve pourraient participer à l’hypersécrétion des hormones incrétines. L’ensemble de ces mécanismes pourrait contribuer à améliorer le contrôle de la glycémie. Enfin, le mini-bypass chez le rat a induit une malabsorption protéique et des fuites énergétiques majeures qui n’étaient pas compensées par l’hyperplasie intestinale ou l’augmentation de l’expression des transporteurs de peptides. Cette thèse montre l’importance du tractus gastro-intestinal dans les conséquences métaboliques de la chirurgie bariatriqueIn today’s global epidemic of obesity, more and more people are undergoing bariatric surgery, which is the best known treatment available to lose weight and treat obesity-associated diseases. Yet, little is known about gastrointestinal (GI) adaptation and its metabolic consequences after surgery. We developed original models of Roux-en-Y gastric bypass (RYGB), mini-bypass (MGB) and vertical sleeve gastrectomy (VSG) in rats, and we characterized the morphological and functional adaptations of the GI epithelium after these surgeries in order to understand the origin of the observed metabolic improvements. We reported profound changes in the remaining gastric mucosa of rats having undergone RYGB and VSG, suggesting an increase in acid production by parietal cells and an impaired production of gastrin and ghrelin. In RYGB rats and patients, the alimentary limb was hyperplasic and intestinal glucose consumption was increased. After VSG, the absorption of glucose during meals appeared diminished. These adaptations could participate in the lowering of blood glucose after surgery. In addition, the increased number of enteroendocrine cells observed in RYGB rats and patients, and their increased density in VSG rats, could contribute to the higher secretion of incretin hormone and improved glycemic control in operated individuals. Finally, we demonstrated in rats that the MGB was more malabsorptive than the RYGB. Indeed, we observed an increased fecal loss of nitrogen and energy despite intestinal overgrowth and higher expression of peptide transporters. This thesis brings new insight to the role of the GI tract in the metabolic outcomes of bariatric surgerie

Intestinal Adaptations after Bariatric Surgery: Consequences on Glucose Homeostasis

International audienceThe gastrointestinal (GI) tract can play a direct role in glucose homeostasis by modulating the digestion and absorption of carbohydrates and by producing the incretin hormones. In recent years, numerous studies have focused on intestinal adaptation following bariatric surgeries. Changes in the number of incretin- (GLP-1, GIP) producing cells have been reported which could result in the modified hormonal response seen after surgery. Additionally, the rate of absorption and the intestinal regions exposed to sugars may affect the time course of appearance of glucose in the blood. This review gives new insights into the direct role of the GI tract in the metabolic outcomes of bariatric surgery, in the context of glucose homeostasis

Reply to Pattou et al. GASTRO-D-16-00421

International audienceWe thank Pattou, Daoudi and Baud for their interest in our work 1 , as well as for their complementary work 2 , on intestinal absorption of ingested glucose after Roux-en-Y Gastric Bypass (RYGB). Based on their recent data obtained with a minipig model of RYGB, they claim this bariatric surgery to affect postprandial glucose metabolism primarily by modulating sodium-glucose intestinal cotransport. They further propose this hypothesis as an " alternative explanation " of our previous data obtained in a rat model and in human subjects who underwent RYGB surgery. First of all, and contrary to what is stated in the above Letter, we never concluded in Cavin et al. 1 that " RYGB does not modify the uptake of ingested glucose ". Our ex vivo studies on intestinal transport revealed that greater amounts of ingested glucose remain within the Roux limb mucosa, as shown by increased luminal glucose uptake and increased SGLT-1 activity when compared to sham rats 1. In vivo, such a retention may result in a reduced transfer of ingested glucose to the blood

Intestinal adaptations following bariatric surgery: towards the identification of new pharmacological targets for obesity-related metabolic diseases

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Malabsorption and Intestinal Adaptation After One Anastomosis Gastric Bypass compared to Roux-en-Y Gastric Bypass in Rats : Protein malabsorption after Mini Gastric Bypass

International audienceThe technically easier one-anastomosis (mini) gastric bypass (MGB) is associated with similar metabolic improvements and weight loss as the Roux-en-Y gastric bypass (RYGB). However, MGB is controversial and suspected to result in greater malabsorption than RYGB.In this study, we compared macronutrient absorption and intestinal adaptation after MGB or RYGB in rats. Body weight and food intake were monitored and glucose tolerance tests were performed in rats subjected to MGB, RYGB, or sham surgery. Carbohydrate, protein, and lipid absorption was determined by fecal analyses. Intestinal remodeling was evaluated by histology and immunohistochemistry. Peptide and amino acid transporter mRNA levels were measured in the remodeled intestinal mucosa and those of anorexigenic and orexigenic peptides in the hypothalamus. The MGB and RYGB surgeries both resulted in a reduction of body weight and an improvement of glucose tolerance relative to sham rats. Hypothalamic orexigenic neuropeptide gene expression was higher in MGB rats than in RYGB or sham rats. Fecal losses of calories and proteins were greater after MGB than RYGB or sham surgery. Intestinal hyperplasia occurred after MGB and RYGB with increased jejunum diameter, higher villi, and deeper crypts than in sham rats. Peptidase and peptide or amino acid transporter genes were overexpressed in jejunal mucosa from MGB rats but not RYGB rats. In rats, MGB led to greater protein malabsorption and energy loss than RYGB. This malabsorption was not compensated by intestinal overgrowth and increased expression of peptide transporters in the jejunum

Effet de la chirurgie bariatrique sur la biodisponibilité des protéines chez le rat obèse

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Effect of Gastric By-pass on Dietary Protein Bioavailability and Protein Anabolism in Rats

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