[Epub ahead of print]
GLP-1R Agonism Enhances Adjustable Gastric Banding In Diet-Induced Obese Rats.
Habegger KM, Kirchner H, Yi CX, Heppner KM, Sweeney D, Ottaway N, Holland J, Amburgy S, Raver C, Krishna R, Müller TD, Perez-Tilve D, Pfluger PT, Obici S, Dimarchi RD, D’Alessio DA, Seeley RJ, Tschöp MH.
Source
Metabolic Disease Institute, Div. of Endocrinology, Diabetes and Metabolism, Dept. of Medicine, University of Cincinnati, Cincinnati OH, USA.
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 more than adjustable gastric banding (AGB), which does not trigger increased GLP-1 secretion. Since GLP-1-based drugs consistently reduce body weight, 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 un-inflated) compared to vehicle-treated animals. Subsequent band inflation was ineffective in vehicle-treated rats, but enhanced weight loss stimulated by GLP1-R agonism. In contrast, there were 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 GLP1-R agonism, offering 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.
- PMID:
23775764
[PubMed – as supplied by publisher]