title: 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.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Metabolic Disease Institute, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Habegger
authors.forename: Henriette
authors.initials: H
authors.lastname: Kirchner
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yi
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Heppner
authors.forename: Dan
authors.initials: D
authors.lastname: Sweeney
authors.forename: Nickki
authors.initials: N
authors.lastname: Ottaway
authors.forename: Jenna
authors.initials: J
authors.lastname: Holland
authors.forename: Sarah
authors.initials: S
authors.lastname: Amburgy
authors.forename: Christine
authors.initials: C
authors.lastname: Raver
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Krishna
authors.forename: Timo D
authors.initials: TD
authors.lastname: Müller
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.forename: Paul T
authors.initials: PT
authors.lastname: Pfluger
authors.forename: Silvana
authors.initials: S
authors.lastname: Obici
authors.forename: Richard D
authors.initials: RD
authors.lastname: DiMarchi
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D000077270:Exenatide; D015390:Gastric Bypass; D015391:Gastroplasty; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D007150:Immunohistochemistry; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000601:surgery*; D010455:Peptides / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D043882:Receptors, Cannabinoid / Q000378:metabolism; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000627:therapeutic use
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D043882:Receptors, Cannabinoid; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide