Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, Ohio.
Diabetes. 2013 Sep;62(9):3261-7. doi: 10.2337/db13-0117. Epub 2013 Jun 17.
Bariatric procedures vary in efficacy, but overall are more effective than behavioral and pharmaceutical treatment. Roux-en-Y gastric bypass causes increased secretion of glucagon-like peptide 1 (GLP-1) and reduces body weight (BW) more than adjustable gastric banding (AGB), which does not trigger increased GLP-1 secretion. Since GLP-1-based drugs consistently reduce BW, we hypothesized that GLP-1 receptor (GLP-1R) agonists would augment the effects of AGB. Male Long-Evans rats with diet-induced obesity received AGB implantation or sham surgery. GLP-1R agonism, cannabinoid receptor-1 (CB1-R) antagonism, or vehicle was combined with inflation to evaluate interaction between AGB and pharmacological treatments. GLP1-R agonism reduced BW in both sham and AGB rats (left uninflated) compared with vehicle-treated animals. Subsequent band inflation was ineffective in vehicle-treated rats but enhanced weight loss stimulated by GLP1-R agonism. In contrast, there was no additional BW loss when CB1-R antagonism was given with AGB. We found band inflation to trigger neural activation in areas of the nucleus of the solitary tract known to be targeted by GLP-1R agonism, offering a potential mechanism for the interaction. These data show that GLP-1R agonism, but not CB1-R antagonism, improves weight loss achieved by AGB and suggest an opportunity to optimize bariatric surgery with adjunctive pharmacotherapy.
减重手术的疗效各异，但总体而言，其效果优于行为和药物治疗。Roux-en-Y 胃旁路手术会增加胰高血糖素样肽 1（GLP-1）的分泌，并比可调节胃束带术（AGB）更有效地减轻体重（BW），AGB 不会引发 GLP-1 的分泌增加。由于基于 GLP-1 的药物能持续减轻 BW，我们假设 GLP-1 受体（GLP-1R）激动剂将增强 AGB 的效果。接受饮食诱导肥胖的雄性 Long-Evans 大鼠接受 AGB 植入或假手术。将 GLP-1R 激动剂、大麻素受体 1（CB1-R）拮抗剂或载体与充气相结合，以评估 AGB 与药物治疗之间的相互作用。与接受载体治疗的动物相比，GLP1-R 激动剂可降低假手术和 AGB 大鼠（未充气）的 BW。随后，在接受载体治疗的大鼠中，充气无效，但增强了 GLP1-R 激动剂刺激的体重减轻。相比之下，当用 AGB 给予 CB1-R 拮抗剂时，BW 没有额外减轻。我们发现，充气会触发孤束核中已知被 GLP-1R 激动剂靶向的区域的神经激活，这为这种相互作用提供了一个潜在的机制。这些数据表明，GLP-1R 激动剂而非 CB1-R 拮抗剂可改善 AGB 实现的体重减轻，并为辅助药物治疗优化减重手术提供了机会。
