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

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.

A comparison of rodent models of vertical sleeve gastrectomy.

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.