PDF(Pubmed)
Abstract：
OBJECTIVE: Bariatric surgery is an effective treatment to obesity, leading to weight loss and improvement in glycemia, that is characterized by hypersecretion of gastrointestinal hormones. However, weight regain and relapse of hyperglycemia are not uncommon. We set to identify mechanisms that can enhance gastrointestinal hormonal secretion following surgery to sustain weight loss.
METHODS: We investigated the effect of somatostatin (Sst) inhibition on the outcomes of bariatric surgery using a mouse model of sleeve gastrectomy (SG).
RESULTS: Sst knockout (sst-ko) mice fed with a calorie-rich diet gained weight normally and had a mild favorable metabolic phenotype compared to heterozygous sibling controls, including elevated plasma levels of GLP-1. Mathematical modeling of the feedback inhibition between Sst and GLP-1 showed that Sst exerts its maximal effect on GLP-1 under conditions of high hormonal stimulation, such as following SG. Obese sst-ko mice that underwent SG had higher levels of GLP-1 compared with heterozygous SG-operated controls. The SG-sst-ko mice regained less weight than controls and maintained lower glycemia months after surgery. Obese wild-type mice that underwent SG and were treated daily with a Sst receptor inhibitor for two months had higher GLP-1 levels, regained less weight, and improved metabolic profile compared to saline-treated SG-operated controls, and compared to inhibitor or saline-treated sham-operated obese mice.
CONCLUSIONS: Our results suggest that inhibition of Sst signaling enhances the long-term favorable metabolic outcomes of bariatric surgery.
METHODS: We investigated the effect of somatostatin (Sst) inhibition on the outcomes of bariatric surgery using a mouse model of sleeve gastrectomy (SG).
RESULTS: Sst knockout (sst-ko) mice fed with a calorie-rich diet gained weight normally and had a mild favorable metabolic phenotype compared to heterozygous sibling controls, including elevated plasma levels of GLP-1. Mathematical modeling of the feedback inhibition between Sst and GLP-1 showed that Sst exerts its maximal effect on GLP-1 under conditions of high hormonal stimulation, such as following SG. Obese sst-ko mice that underwent SG had higher levels of GLP-1 compared with heterozygous SG-operated controls. The SG-sst-ko mice regained less weight than controls and maintained lower glycemia months after surgery. Obese wild-type mice that underwent SG and were treated daily with a Sst receptor inhibitor for two months had higher GLP-1 levels, regained less weight, and improved metabolic profile compared to saline-treated SG-operated controls, and compared to inhibitor or saline-treated sham-operated obese mice.
CONCLUSIONS: Our results suggest that inhibition of Sst signaling enhances the long-term favorable metabolic outcomes of bariatric surgery.
摘要：
减肥手术是一种有效的肥胖治疗方法，导致体重减轻和血糖改善，其特征是胃肠激素分泌过多。然而,体重恢复和高血糖复发并不少见.这里,我们使用袖状胃切除术(SG)小鼠模型研究了生长抑素(Sst)在减重手术结局中的作用.与杂合同胞对照相比，饲喂富含卡路里饮食的Sst敲除（sst-ko）小鼠的体重增加正常，并且具有轻度有利的代谢表型，包括血浆GLP-1水平升高。Sst和GLP-1之间反馈抑制的数学模型表明，在高激素刺激的条件下，Sst对GLP-1发挥最大作用。比如跟随SG。的确,接受SG的肥胖sst-ko小鼠的GLP-1水平高于接受SG手术的杂合子对照.SG-sst-ko小鼠的体重比对照组恢复得更低，并且在手术后几个月保持较低的血糖。接受SG并每天用Sst受体抑制剂治疗两个月的肥胖野生型小鼠的GLP-1水平较高，恢复了较少的体重，与盐水处理的SG手术对照相比，改善了代谢状况，并与抑制剂或盐水处理的假手术肥胖小鼠进行比较。我们的结果表明，抑制Sst信号可增强减肥手术的长期有利代谢结果。
