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Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy.

ABSTRACT: Obesity has profound negative consequences on female reproduction as well as on the metabolic health of offspring. Bariatric surgery is the most effective method for sustained weight loss. A critical question is whether bariatric surgery can reverse the deleterious effects of obesity on both female reproduction and subsequent offspring. Vertical sleeve gastrectomy (VSG) is a bariatric procedure rapidly growing in popularity because it provides weight loss and other metabolic benefits that are comparable to those offered by the more complicated Roux-en-Y gastric bypass (RYGB). Female rats rendered obese on a high-fat diet (HFD) underwent either VSG or sham surgery. Like their male counterparts, females had significant metabolic improvements including reduced adiposity and improved glucose tolerance. After VSG, female rats showed a more normal reproductive cycle. Despite these maternal benefits, the offspring of dams receiving VSG were born smaller and lighter than offspring of control dams that underwent sham surgery. When maintained on an HFD after puberty, these adult offspring had a greater propensity to develop glucose intolerance and increased adiposity than the offspring of lean mothers or obese mothers who underwent sham surgery. These data suggest that weight loss alone by obese mothers is not sufficient to reverse the deleterious effects of an HFD and obesity on their offspring.

SUBMITTER: Grayson BE

PROVIDER: S-EPMC3939702 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy.

Grayson Bernadette E BE Schneider Katarina M KM Woods Stephen C SC Seeley Randy J RJ

Science translational medicine 20130801 199

Obesity has profound negative consequences on female reproduction as well as on the metabolic health of offspring. Bariatric surgery is the most effective method for sustained weight loss. A critical question is whether bariatric surgery can reverse the deleterious effects of obesity on both female reproduction and subsequent offspring. Vertical sleeve gastrectomy (VSG) is a bariatric procedure rapidly growing in popularity because it provides weight loss and other metabolic benefits that are co ...[more]

PMID: 23966301

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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.

Dataset Information

Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy.

Publications

Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy.

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