GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats

Diabetes. 2013 Sep;62(9):3261-7. doi: 10.2337/db13-0117. Epub 2013 Jun 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition / drug effects
  • Eating / drug effects
  • Exenatide
  • Gastric Bypass
  • Gastroplasty
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor
  • Immunohistochemistry
  • Male
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / surgery*
  • Peptides / therapeutic use
  • Rats
  • Rats, Long-Evans
  • Receptors, Cannabinoid / metabolism
  • Receptors, Glucagon / agonists*
  • Venoms / therapeutic use

Substances

  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Peptides
  • Receptors, Cannabinoid
  • Receptors, Glucagon
  • Venoms
  • Glucagon-Like Peptide 1
  • Exenatide