GLP-1R Agonism Enhances Adjustable Gastric Banding in Diet-Induced Obese Rats

  1. Matthias H. Tschöp2
  1. 1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, Ohio
  2. 2Institute for Diabetes and Obesity, Helmholtz Zentrum München and Technische Universität München, Munich, Germany
  3. 3Department of Chemistry, Indiana University, Bloomington, Indiana
  1. Corresponding author: Matthias H. Tschöp, matthias.tschoep{at}helmholtz-muenchen.de.

Abstract

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.

  • Received January 23, 2012.
  • Accepted June 10, 2013.

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  1. Diabetes vol. 62 no. 9 3261-3267
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