New methodsExperimental endoscopyGastric mucosal devitalization is safe and effective in reducing body weight and visceral adiposity in a porcine model
Introduction
The worldwide prevalence of overweight and obesity in children, adolescents, and adults has reached pandemic proportions.1 Metabolic surgery, such as Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), is the most effective and durable weight loss and metabolic therapy.2, 3 Metabolic surgery alters the physiologic regulation of body fat mass, demonstrating the critical role of the GI tract in the regulation of metabolic function.4 The mechanisms of action are neither mechanical restriction nor macronutrient malabsorption and remain poorly understood.5, 6 Furthermore, there appears to be weight-dependent and weight-independent mechanisms of action.7, 8 Unfortunately, because of its invasiveness and irreversibility, metabolic surgery is severely underused.9 The development of minimally invasive flexible endoscopic methods to mimic the effect of metabolic surgery provides an opportunity to fulfill the large unmet need.10
The primary site of regulation of glucose and lipid metabolism remains ambiguous. Human and rodent studies of RYGB allude to the importance of bypassing the duodenum.11 Conversely, SG does not alter nutrient flow across the duodenum yet induces similar metabolic effects to RYGB, signifying that the stomach may be a critical regulator of glucose and lipid homeostasis.2, 5 Some have proposed that the accelerated nutrient transit through the GI tract seen with SG causes more undigested nutrients to reach the distal ileum resulting in postprandial increase in glucagon-like Peptide 1; however, mechanistic evidence for this is lacking.12 A common element to both surgeries is the exclusion or resection of the gastric mucosa, an often-underappreciated neuroendocrine organ.13, 14, 15
Our group has been investigating the hypothesis that excision of the gastric mucosa is a key contributor to the improvement in obesity-related comorbidities perceived after SG.16, 17 We previously demonstrated, in an obese rat model, that the gastric mucosa is an independent regulator of glucose and lipid metabolism.18 In that study, gastric mucosal devitalization (GMD) reduced body weight and visceral adiposity, improved serum lipid and glucose profiles, and reduced liver lipid content.18 Considering those promising results, our goal was to translate our technique of GMD into a large animal model to assess its technical feasibility, efficacy, and safety. The porcine model was chosen because it has similar GI anatomy to humans and allows utilization of commercially available endoscopic equipment. Furthermore, porcine models are a familiar platform to investigate endoscopic bariatric therapies before pilot clinical studies.19, 20
Section snippets
Study design
We performed a 3-arm prospective randomized controlled trial with an 8-week follow-up period. A total of 23 healthy litter-matched male German saddleback pigs aged 11 weeks and weighing 30 to 35 kg were obtained from a commercial, closed-herd pig vendor (Lehr- und Versuchsgut Oberholz, Großpösna, Saxony, Germany). This breed of domestic pig was chosen because of their relatively high body fat mass. Two pigs underwent GMD; one was killed immediately after the procedure and the other at 4 weeks
Technical feasibility and safety
All 23 pigs successfully underwent and survived their designated interventions and were killed per protocol. There were no changes in physiologic parameters observed during or after the intervention, including electrocardiogram, heart rate, respiration rate, temperature, blood pressure, and oxygen saturation. There were no intra- or post-procedural adverse events observed. The animals were upright, alert, responsive, defecating, urinating, drinking, and tolerating oral intake within 24 hours
Discussion
The obesity pandemic, being a global public health concern, has appropriately captured the attention of the major GI societies.29 Furthermore, as the GI tract is a critical metabolic regulator of obesity and its metabolic comorbidities, GI endoscopy societies have taken special initiatives to assess currently available and future endobariatric therapies.30 Although weight reduction is an important outcome, a disproportionate emphasis has been placed on it as opposed to improvements in
Acknowledgments
The study was supported by Erbe Elektromedizin GmbH, Tübingen, Germany.
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2020, Gastrointestinal EndoscopyCitation Excerpt :The best results were demonstrated when 2 clips were placed on opposite sides of the GJA, reducing the outlet diameter by more than 80%.61 Circumferential application of APC to the GJA with varying technique has been reported to induce scarring and/or mucosal devitalization, with a subsequent reduction in the anastomotic diameter that promotes weight loss.62-67 The first reported study prospectively evaluated 30 patients who underwent 3 sessions of APC 8 weeks apart.
Are We Moving in the Right Direction by Altering Gastric Motility for Weight Loss?
2020, Clinical Gastroenterology and HepatologyGastrointestinal Endoscopy Editorial Board top 10 topics: advances in GI endoscopy in 2018
2019, Gastrointestinal EndoscopyCitation Excerpt :Reports on the rather controversial endoscopic treatment of weight regain after gastric bypass continued to be published in 2018, with 1 nonrandomized study comparing an interrupted suture technique with a purse-string suture technique for transoral outlet reduction in 241 patients reporting significant weight loss for both techniques in patients who had regained weight after surgical gastric bypass.15 The year 2018 also was notable for multiple publications on the use of endoscopic ablation techniques for metabolic interventions (eg, type 2 diabetes).16,17 These “explorative” investigations are interesting both from their creativity but also as they reflect our increasing understanding of the role of digestive hormones on metabolic diseases18 and the increasing contributions made by endoscopists to the battle against obesity.
Endoluminal bariatric and metabolic therapies: State-of-the-art
2023, Current Opinion in Gastroenterology
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DISCLOSURE: Dr Kumbhari is a consultant for Boston Scientific, Apollo Endosurgery, ReShape Life Sciences, and Medtronic. Dr Enderle is the vice president of research and an employee of Erbe GmbH Germany. Dr Khashab is a consultant for Boston Scientific and Olympus America. Dr Kalloo is a founding Member, equity Holder, and consultant for Apollo Endosurgery. All other authors disclosed no financial relationships relevant to this publication.