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

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

doi:10.2337/db13-0117

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

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

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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-1based 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.

Original language	English
Pages (from-to)	3261-3267
Number of pages	7
Journal	Diabetes
Volume	62
Issue number	9
DOIs	https://doi.org/10.2337/db13-0117
State	Published - Sep 2013
Externally published	Yes

Funding

Funders	Funder number
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK093848
National Institute of Diabetes and Digestive and Kidney Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/db13-0117

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Habegger, K. M., Kirchner, H., Yi, C. X., Heppner, K. M., Sweeney, D., Ottaway, N., Holland, J., Amburgy, S., Raver, C., Krishna, R., Müller, T. D., Perez-Tilve, D., Pfluger, P. T., Obici, S., DiMarchi, R. D., D'Alessio, D. A., Seeley, R. J., & Tschöp, M. H. (2013). GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats. Diabetes, 62(9), 3261-3267. https://doi.org/10.2337/db13-0117

@article{d91dee78316f4df2a1d6c2fccbe88922,

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-1based 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.",

author = "Habegger, {Kirk M.} and Henriette Kirchner and Yi, {Chun Xia} and Heppner, {Kristy M.} and Dan Sweeney and Nickki Ottaway and Jenna Holland and Sarah Amburgy and Christine Raver and Radhakrishna Krishna and M{\"u}ller, {Timo D.} and Diego Perez-Tilve and Pfluger, {Paul T.} and Silvana Obici and DiMarchi, {Richard D.} and D'Alessio, {David A.} and Seeley, {Randy J.} and Tsch{\"o}p, {Matthias H.}",

year = "2013",

month = sep,

doi = "10.2337/db13-0117",

language = "English",

volume = "62",

pages = "3261--3267",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "9",

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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 2013, 'GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats', Diabetes, vol. 62, no. 9, pp. 3261-3267. https://doi.org/10.2337/db13-0117

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T1 - GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats

AU - Habegger, Kirk M.

AU - Kirchner, Henriette

AU - Yi, Chun Xia

AU - Heppner, Kristy M.

AU - Sweeney, Dan

AU - Ottaway, Nickki

AU - Holland, Jenna

AU - Amburgy, Sarah

AU - Raver, Christine

AU - Krishna, Radhakrishna

AU - Müller, Timo D.

AU - Perez-Tilve, Diego

AU - Pfluger, Paul T.

AU - Obici, Silvana

AU - DiMarchi, Richard D.

AU - D'Alessio, David A.

AU - Seeley, Randy J.

AU - Tschöp, Matthias H.

PY - 2013/9

Y1 - 2013/9

N2 - 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-1based 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.

AB - 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-1based 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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SP - 3261

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JO - Diabetes

JF - Diabetes

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ER -

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

Abstract

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UN SDGs

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