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

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.

• Authors: Kirk M Habegger, Henriette Kirchner, Chun-Xia Yi, Kristy M Heppner, Dan Sweeney, Nickki Ottaway, Jenna Holland, Sarah Amburgy, Christine Raver, Radhakrishna Krishna, Timo D Müller, Diego Perez-Tilve, Paul T Pfluger, Silvana Obici, Richard D DiMarchi, David A D'Alessio, Randy J Seeley, Matthias H Tschöp
• Journal: Diabetes (Diabetes) Vol. 62 Issue 9 Pg. 3261-7 (Sep 2013) ISSN: 1939-327X [Electronic] United States
• PMID: 23775764 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, etiology, metabolism, surgery)
• Peptides (therapeutic use)
• Rats
• Rats, Long-Evans
• Receptors, Cannabinoid (metabolism)
• Receptors, Glucagon (agonists)
• Venoms (therapeutic use)