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:https://doi.org/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

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

20 Citations (Scopus)

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

Original language	English
Pages (from-to)	3261-3267
Journal	Diabetes
Volume	62
Issue number	9
DOIs	https://doi.org/10.2337/db13-0117
Publication status	Published - 2013

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https://doi.org/10.2337/db13-0117

Cite this

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{67226b51f6334558b5744d31c674cf4f,

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",

author = "Habegger, {Kirk M.} and Henriette Kirchner and Chun-Xia Yi 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",

doi = "https://doi.org/10.2337/db13-0117",

language = "English",

volume = "62",

pages = "3261--3267",

journal = "Diabetes",

issn = "0012-1797",

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Habegger, KM, Kirchner, H, Yi, C-X, 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

Y1 - 2013

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-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

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-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

U2 - https://doi.org/10.2337/db13-0117

DO - https://doi.org/10.2337/db13-0117

M3 - Article

C2 - 23775764

SN - 0012-1797

VL - 62

SP - 3261

EP - 3267

JO - Diabetes

JF - Diabetes

IS - 9

ER -