Dataset Information

Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy.

ABSTRACT: Vertical sleeve gastrectomy (VSG), the most utilized bariatric procedure in clinical practice, greatly reduces body weight and improves a variety of metabolic disorders. However, one of its long-term complications is bone loss and increased risk of fracture. Elevated circulating sclerostin (SOST) and granulocyte-colony stimulating factor (G-CSF) concentrations have been considered as potential contributors to VSG-associated bone loss. To test these possibilities, we administrated antibodies to SOST or G-CSF receptor and investigated alterations to bone and marrow niche following VSG. Neutralizing either SOST or G-CSF receptor did not alter beneficial effects of VSG on adiposity and hepatic steatosis, and anti-SOST treatment provided a further improvement to glucose tolerance. SOST antibodies partially reduced trabecular and cortical bone loss following VSG by increasing bone formation, whereas G-CSF receptor antibodies had no effects on bone mass. The expansion in myeloid cellularity and reductions in bone marrow adiposity seen with VSG were partially eliminated by treatment with Anti-G-CSF receptor. Taken together, these experiments demonstrate that antibodies to SOST or G-CSF receptor may act through independent mechanisms to partially block effects of VSG on bone loss or marrow niche cells, respectively.

SUBMITTER: Li Z

PROVIDER: S-EPMC10513354 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy.

Li Ziru Z Qiu Kevin K Zhao Jingtong J Granger Katrina K Yu Hui H Lewis Alfor G AG Myronovych Andriy A Toure Mouhamadoul H MH Hatsell Sarah J SJ Economides Aris N AN Seeley Randy J RJ MacDougald Ormond A OA

Bone 20230126

Vertical sleeve gastrectomy (VSG), the most utilized bariatric procedure in clinical practice, greatly reduces body weight and improves a variety of metabolic disorders. However, one of its long-term complications is bone loss and increased risk of fracture. Elevated circulating sclerostin (SOST) and granulocyte-colony stimulating factor (G-CSF) concentrations have been considered as potential contributors to VSG-associated bone loss. To test these possibilities, we administrated antibodies to S ...[more]

PMID: 36709915

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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

Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy.

Publications

Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy.

Similar Datasets

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