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

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 9; pp. 3261 - 3267
• Main Authors: HABEGGER, Kirk M, KIRCHNER, Henriette, MÜLLER, Timo D, PEREZ-TILVE, Diego, PFLUGER, Paul T, OBICI, Silvana, DIMARCHI, Richard D, D'ALESSIO, David A, SEELEY, Randy J, TSCHOP, Matthias H, YI, Chun-Xia, HEPPNER, Kristy M, SWEENEY, Dan, OTTAWAY, Nickki, HOLLAND, Jenna, AMBURGY, Sarah, RAVER, Christine, KRISHNA, Radhakrishna
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2013
• Subjects: Animals; Bariatric surgery; Biological and medical sciences; Body Composition - drug effects; Care and treatment; Complications and side effects; Diabetes. Impaired glucose tolerance; Diet; Eating - drug effects; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gastric Bypass; Gastrointestinal surgery; Gastroplasty; Genetic aspects; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide-1 Receptor; Health aspects; Immunohistochemistry; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - drug therapy; Obesity - etiology; Obesity - metabolism; Obesity - surgery; Original Research; Patient outcomes; Peptides; Peptides - therapeutic use; Physiological aspects; Rats; Rats, Long-Evans; Receptors, Cannabinoid - metabolism; Receptors, Glucagon - agonists; Rodents; Surgery; Venoms - therapeutic use; Weight loss; United States; Endocrinopathy; Stomach; Obesity; Rat; Digestive system; Diabetes mellitus; Rodentia; Nutrition disorder; Feeding; Vertebrata; Mammalia; Diet; Animal; Nutritional status
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db13-0117

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.