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A comparison of rodent models of vertical sleeve gastrectomy.

ABSTRACT: BACKGROUND:Although vertical sleeve gastrectomy (VSG) is fashioned in humans by applying multiple staple loads, rodent VSG is generally created through a single-staple load application. OBJECTIVES:To investigate the impact of a 2-staple load VSG rat model more closely resembling the multistaple load operation done in humans on weight, metabolic outcomes, and the microbiome and how these compare with those obtained with the standard one-staple load model. SETTING:University research facility, United States. METHODS:High-fat diet-induced obese male rats were randomized to single-staple load VSG (VSG1), 2-staple load VSG (VSG2), or sham operation (Sham). Outcomes included weight and composition, food intake, glucose metabolism, lipids, bile acids, and intestinal microbiome. Statistical comparisons were performed using analysis of variance. RESULTS:Both procedures resulted in substantial weight and body fat loss compared with Sham-treated animals. Weight loss was modestly greater for VSG2 compared with VSG1. Food intake was reduced in both procedures and accounted for the observed weight reduction. Glucose tolerance and plasma and hepatic lipid profiles were improved comparably in VSG1 and VSG2 relative to Sham. Bile acids were higher for VSG2 compared with Sham but not significantly different between VSG1 and VSG2. Neither procedure impacted intestinal microbiome richness and diversity compared with Sham across multiple intestinal sections. Colonic Actinobacteria was more abundant in VSG2 than in Sham. Relative abundances of bacterial phyla did not differ among VSG1, VSG2, and Sham across the remaining intestinal sections. CONCLUSIONS:Although VSG1 or VSG2 offer effective and overall comparable platforms for the study of obesity, VSG2 resulted in superior weight loss.

SUBMITTER: Alvarez R

PROVIDER: S-EPMC6242744 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A comparison of rodent models of vertical sleeve gastrectomy.

Alvarez Rafael R Lewis Alfor G AG Toure Mouhamadoul H MH Seeley Randy J RJ

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 20180702 10

<h4>Background</h4>Although vertical sleeve gastrectomy (VSG) is fashioned in humans by applying multiple staple loads, rodent VSG is generally created through a single-staple load application.<h4>Objectives</h4>To investigate the impact of a 2-staple load VSG rat model more closely resembling the multistaple load operation done in humans on weight, metabolic outcomes, and the microbiome and how these compare with those obtained with the standard one-staple load model.<h4>Setting</h4>University ...[more]

PMID: 30093310

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Project description:ObjectiveBariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model.MethodsDiet-induced obese male Sprague-Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals.ResultsFollowing VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus.ConclusionsCollectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Project description:Bariatric surgery is the most effective treatment for obesity and its comorbidities. However, our understanding of the molecular mechanisms behind its beneficial effects is limited. Extracellular vesicles (EVs) comprise an important mode of intercellular communication. They carry nucleic acids, hormones, and signaling molecules and regulate multiple processes. Our aim was to test the role of EVs in the effects of vertical sleeve gastrectomy (VSG) using a mouse model. Small intestinal EVs were obtained from the mice that underwent VSG or control surgery and were on chow or high-fat diet or diet-restricted, and then they were subjected to the proteomic analysis. Enteroid and bacterial cultures were treated with EVs to evaluate their survival effect. A mouse cohort received intraduodenal administration of EVs from VSG or Sham mice for 10 days. Body weight, glucose metabolism, and intestinal morphology were evaluated. EVs were enriched in the intestinal lumen and mucus of VSG compared with Sham mice. Protein composition of VSG and Sham-derived EVs was highly distinct. When introduced into culture, VSG EVs decreased survival of intestinal enteroids and, conversely, promoted proliferation of bacteria. Mice administered with EVs obtained from VSG and Sham groups did not show differences in body weight, food intake, or glucose metabolism. Intestinal morphology was altered, as VSG EVs caused reduction of ileal villi length and decreased epithelial proliferation in the jejunum and ileum. VSG causes remodeling of intestinal EVs, which results in unique protein composition. VSG-derived EVs exhibit cytotoxic effects on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.NEW & NOTEWORTHY This is the first study that investigates the impact of bariatric surgery on protein composition of intestinal extracellular vesicles. Extracellular vesicle composition is greatly altered after vertical sleeve gastrectomy and may potentially modulate various signaling pathways. In our study, extracellular vesicles from vertical sleeve gastrectomy-treated mice promote bacterial proliferation but exhibit cytotoxic effect on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.

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A comparison of rodent models of vertical sleeve gastrectomy.

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A comparison of rodent models of vertical sleeve gastrectomy.

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