Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study

E. van Duinkerken; G. Bernardes; L. van Bloemendaal; D.J. Veltman; F. Barkhof; D.C. Mograbi; V.E.A. Gerdes; C.F. Deacon; J.J. Holst; M.L. Drent; M. Diamant; J. ten Kulve; R.G. Ijzerman

doi:10.1111/dom.14233

Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study

E. van Duinkerken
, G. Bernardes
, L. van Bloemendaal
, D.J. Veltman
, F. Barkhof
, D.C. Mograbi
, V.E.A. Gerdes
, C.F. Deacon
, J.J. Holst
, M.L. Drent
, M. Diamant
, J. ten Kulve
, R.G. Ijzerman

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

Abstract

Aim: To assess the effects of Roux-en-Y gastric bypass surgery (RYGB)-related changes in glucagon-like peptide-1 (GLP-1) on cerebral resting-state functioning in obese women.

Materials and Methods: In nine obese females aged 40-54 years in the fasted state, we studied the effects of RYGB and GLP-1 on five a priori selected networks implicated in food- and reward-related processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate and anterior cingulate/orbitofrontal networks).

Results: Before surgery, GLP-1 receptor blockade (using exendin9-39) was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared with placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLP-1 receptor blockade had a larger effect on connectivity in this region than GLP-1 receptor blockade before RYGB (all PFWE <.05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in body mass index and food scores after RYGB.

Conclusions: These findings suggest GLP-1 involvement in resting-state networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLP-1–induced changes in resting-state connectivity in RYGB-mediated weight loss and appetite control.

Original language	English
Pages (from-to)	415-424
Number of pages	10
Journal	Diabetes, Obesity and Metabolism
Volume	23
Issue number	2
Early online date	20 Oct 2020
DOIs	https://doi.org/10.1111/dom.14233
Publication status	Published - Feb 2021

Bibliographical note

Funding

F.B. is supported by the NIHR Biomedical Research Center at UCLH. C.F.D. has received consultancy/speaker fees from Bristol‐Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis and Novo Nordisk. J.J.H. has received fees for consulting, lecturing and/or being part of an advisory board from AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly and Company, GI Dynamics, Merck Sharp & Dohme, Novo Nordisk, Novartis, Sanofi, Takeda and Zealand Pharma. M.D. was a consultant for Abbott, AstraZeneca, Bristol‐Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, GI Dynamics, Merck Sharp & Dohme, Novo Nordisk, Poxel SA and Sanofi and was a speaker for BristolMyers Squibb/AstraZeneca, Eli Lilly and Company, Novo Nordisk and Sanofi. Through M.D., the VU University Medical Center received research grants from Abbott, Bristol‐Myers Squibb/AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme, Novo Nordisk and Sanofi. R.G.I. is the principal investigator of studies sponsored by research grants from Novo Nordisk and Eli Lilly and Company. M.D. and R.G.I. report receiving no personal payments in connection to the above‐mentioned activities, but all payments were directly transferred to the Diabetes Center (VU University Medical Center) non‐profit research foundation. No other potential conflicts of interest relevant to this article were reported. F.B. is supported by the NIHR Biomedical Research Center at UCLH. F.B. is supported by the National Institute of Health Research Biomedical Research Center at University College London Hospitals. Funding information

Funders
NIHR Biomedical Research Center
National Institute of Health Research Biomedical Research Center at University College London Hospitals
VU University Medical Center
Abbott Laboratories
Bristol-Myers Squibb
Eli Lilly and Company
AstraZeneca
Sanofi
Medtronic
Boehringer Ingelheim
Merck Sharp and Dohme
Novo Nordisk
University College London Hospitals NHS Foundation Trust
UCLH Biomedical Research Centre

UN SDGs

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

SDG 3 Good Health and Well-being

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10.1111/dom.14233

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van Duinkerken, E., Bernardes, G., van Bloemendaal, L., Veltman, D. J., Barkhof, F., Mograbi, D. C., Gerdes, V. E. A., Deacon, C. F., Holst, J. J., Drent, M. L., Diamant, M., ten Kulve, J., & Ijzerman, R. G. (2021). Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study. Diabetes, Obesity and Metabolism, 23(2), 415-424. https://doi.org/10.1111/dom.14233

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title = "Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study",

abstract = "Aim: To assess the effects of Roux-en-Y gastric bypass surgery (RYGB)-related changes in glucagon-like peptide-1 (GLP-1) on cerebral resting-state functioning in obese women. Materials and Methods: In nine obese females aged 40-54 years in the fasted state, we studied the effects of RYGB and GLP-1 on five a priori selected networks implicated in food- and reward-related processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate and anterior cingulate/orbitofrontal networks). Results: Before surgery, GLP-1 receptor blockade (using exendin9-39) was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared with placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLP-1 receptor blockade had a larger effect on connectivity in this region than GLP-1 receptor blockade before RYGB (all PFWE <.05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in body mass index and food scores after RYGB. Conclusions: These findings suggest GLP-1 involvement in resting-state networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLP-1–induced changes in resting-state connectivity in RYGB-mediated weight loss and appetite control.",

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van Duinkerken, E, Bernardes, G, van Bloemendaal, L, Veltman, DJ, Barkhof, F, Mograbi, DC, Gerdes, VEA, Deacon, CF, Holst, JJ, Drent, ML, Diamant, M, ten Kulve, J & Ijzerman, RG 2021, 'Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study', Diabetes, Obesity and Metabolism, vol. 23, no. 2, pp. 415-424. https://doi.org/10.1111/dom.14233

Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study. / van Duinkerken, E.; Bernardes, G.; van Bloemendaal, L. et al.
In: Diabetes, Obesity and Metabolism, Vol. 23, No. 2, 02.2021, p. 415-424.

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

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T1 - Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women

T2 - A proof-of-concept resting-state functional MRI study

AU - van Duinkerken, E.

AU - Bernardes, G.

AU - van Bloemendaal, L.

AU - Veltman, D.J.

AU - Barkhof, F.

AU - Mograbi, D.C.

AU - Gerdes, V.E.A.

AU - Deacon, C.F.

AU - Holst, J.J.

AU - Drent, M.L.

AU - Diamant, M.

AU - ten Kulve, J.

AU - Ijzerman, R.G.

PY - 2021/2

Y1 - 2021/2

N2 - Aim: To assess the effects of Roux-en-Y gastric bypass surgery (RYGB)-related changes in glucagon-like peptide-1 (GLP-1) on cerebral resting-state functioning in obese women. Materials and Methods: In nine obese females aged 40-54 years in the fasted state, we studied the effects of RYGB and GLP-1 on five a priori selected networks implicated in food- and reward-related processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate and anterior cingulate/orbitofrontal networks). Results: Before surgery, GLP-1 receptor blockade (using exendin9-39) was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared with placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLP-1 receptor blockade had a larger effect on connectivity in this region than GLP-1 receptor blockade before RYGB (all PFWE <.05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in body mass index and food scores after RYGB. Conclusions: These findings suggest GLP-1 involvement in resting-state networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLP-1–induced changes in resting-state connectivity in RYGB-mediated weight loss and appetite control.

AB - Aim: To assess the effects of Roux-en-Y gastric bypass surgery (RYGB)-related changes in glucagon-like peptide-1 (GLP-1) on cerebral resting-state functioning in obese women. Materials and Methods: In nine obese females aged 40-54 years in the fasted state, we studied the effects of RYGB and GLP-1 on five a priori selected networks implicated in food- and reward-related processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate and anterior cingulate/orbitofrontal networks). Results: Before surgery, GLP-1 receptor blockade (using exendin9-39) was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared with placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLP-1 receptor blockade had a larger effect on connectivity in this region than GLP-1 receptor blockade before RYGB (all PFWE <.05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in body mass index and food scores after RYGB. Conclusions: These findings suggest GLP-1 involvement in resting-state networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLP-1–induced changes in resting-state connectivity in RYGB-mediated weight loss and appetite control.

U2 - 10.1111/dom.14233

DO - 10.1111/dom.14233

M3 - Article

SN - 1462-8902

VL - 23

SP - 415

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JO - Diabetes, Obesity and Metabolism

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van Duinkerken E, Bernardes G, van Bloemendaal L, Veltman DJ, Barkhof F, Mograbi DC et al. Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study. Diabetes, Obesity and Metabolism. 2021 Feb;23(2):415-424. Epub 2020 Oct 20. doi: 10.1111/dom.14233

Cerebral effects of glucagon-like peptide-1 receptor blockade before and after Roux-en-Y gastric bypass surgery in obese women: A proof-of-concept resting-state functional MRI study

Abstract

Bibliographical note

Funding

UN SDGs

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