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

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:

دوره 62  شماره 

صفحات  -

تاریخ انتشار 2013