RF36 | PSUN93 A Role for Somatostatin in Regulating Weight Regain after Bariatric Surgery in Mice

Abstract Somatostatin is an inhibitory neuropeptide expressed in several neural and endocrine systems. For example, Somatostatin represses the secretion of growth hormone from the pituitary gland, and the secretion of gastrointestinal and pancreatic hormones. It is therefore surprising that Somatostatin knockout (sst-ko) mice have a very mild metabolic phenotype under normal conditions. Here, we studied the role of Somatostatin in weight gain and weight loss using sst-ko mice. We found that sst-ko mice gained weight, lost weight, and regained weight at an equal rate to heterozygous siblings following dietary interventions. However, overweight sst-ko mice did not regain weight after sleeve gastrectomy bariatric surgery compared to heterozygous siblings that underwent the same surgery. This phenotype persisted for three months after surgery, whilst a high-fat high-sucrose diet was provided. Mechanistically, the surgery led to hypersecretion of glucagon-like peptide 1 (Glp1), which was not observed in sham-operated sst-ko mice. Moreover, Glp1 hypersecretion was greater than that of heterozygotes sleeve gastrectomy operated mice. Sleeve gastrectomy sst-ko mice displayed lower levels of fasting insulin, and very rapid response to glucose loading. In conclusion, a metabolic and endocrine phenotype of sst-ko mice was exposed following bariatric surgery. These mice remained lean and increased Glp1 secretion, suggesting that somatostatin has an important role in regulating gastrointestinal hormone secretion, especially following bariatric surgery. Further study is required to determine whether pharmacological inhibition of somatostatin signaling can enhance the outcomes of bariatric surgery in mice and in patients. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:48 p.m. - 12:53 p.m.