GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity. / Falk, Sarah; Petersen, Jonas Odgaard; Svendsen, Charlotte Sashi Aier; Leguizamon, Cesar Ramon Romero; Jørgensen, Søren Heide; Krauth, Nathalie; Ludwig, Mette Q; Lundø, Kathrine; Roostalu, Urmas; Hjort-Gregersen, Grethe Skovbjerg; Nielsen, Duy Anh Gurskov; Ejdrup, Aske Lykke; Pers, Tune H; Dmytriyeva, Oksana; Hecksher-Soerensen, Jacob; Gether, Ulrik; Kohlmeier, Kristi Anne; Clemmensen, Christoffer.

In: Cell Reports, Vol. 42, No. 5, 112466, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Falk, S, Petersen, JO, Svendsen, CSA, Leguizamon, CRR, Jørgensen, SH, Krauth, N, Ludwig, MQ, Lundø, K, Roostalu, U, Hjort-Gregersen, GS, Nielsen, DAG, Ejdrup, AL, Pers, TH, Dmytriyeva, O, Hecksher-Soerensen, J, Gether, U, Kohlmeier, KA & Clemmensen, C 2023, 'GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity', Cell Reports, vol. 42, no. 5, 112466. https://doi.org/10.1016/j.celrep.2023.112466

APA

Falk, S., Petersen, J. O., Svendsen, C. S. A., Leguizamon, C. R. R., Jørgensen, S. H., Krauth, N., Ludwig, M. Q., Lundø, K., Roostalu, U., Hjort-Gregersen, G. S., Nielsen, D. A. G., Ejdrup, A. L., Pers, T. H., Dmytriyeva, O., Hecksher-Soerensen, J., Gether, U., Kohlmeier, K. A., & Clemmensen, C. (2023). GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity. Cell Reports, 42(5), [112466]. https://doi.org/10.1016/j.celrep.2023.112466

Vancouver

Falk S, Petersen JO, Svendsen CSA, Leguizamon CRR, Jørgensen SH, Krauth N et al. GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity. Cell Reports. 2023;42(5). 112466. https://doi.org/10.1016/j.celrep.2023.112466

Author

Falk, Sarah ; Petersen, Jonas Odgaard ; Svendsen, Charlotte Sashi Aier ; Leguizamon, Cesar Ramon Romero ; Jørgensen, Søren Heide ; Krauth, Nathalie ; Ludwig, Mette Q ; Lundø, Kathrine ; Roostalu, Urmas ; Hjort-Gregersen, Grethe Skovbjerg ; Nielsen, Duy Anh Gurskov ; Ejdrup, Aske Lykke ; Pers, Tune H ; Dmytriyeva, Oksana ; Hecksher-Soerensen, Jacob ; Gether, Ulrik ; Kohlmeier, Kristi Anne ; Clemmensen, Christoffer. / GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity. In: Cell Reports. 2023 ; Vol. 42, No. 5.

Bibtex

@article{868ff9538b32436ba30438174f46a1e2,
title = "GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity",
abstract = "Glucagon-like peptide-1 receptor (GLP-1R) agonists promote nicotine avoidance. Here, we show that the crosstalk between GLP-1 and nicotine extends beyond effects on nicotine self-administration and can be exploited pharmacologically to amplify the anti-obesity effects of both signals. Accordingly, combined treatment with nicotine and the GLP-1R agonist, liraglutide, inhibits food intake and increases energy expenditure to lower body weight in obese mice. Co-treatment with nicotine and liraglutide gives rise to neuronal activity in multiple brain regions, and we demonstrate that GLP-1R agonism increases excitability of hypothalamic proopiomelanocortin (POMC) neurons and dopaminergic neurons in the ventral tegmental area (VTA). Further, using a genetically encoded dopamine sensor, we reveal that liraglutide suppresses nicotine-induced dopamine release in the nucleus accumbens in freely behaving mice. These data support the pursuit of GLP-1R-based therapies for nicotine dependence and encourage further evaluation of combined treatment with GLP-1R agonists and nicotinic receptor agonists for weight loss.",
author = "Sarah Falk and Petersen, {Jonas Odgaard} and Svendsen, {Charlotte Sashi Aier} and Leguizamon, {Cesar Ramon Romero} and J{\o}rgensen, {S{\o}ren Heide} and Nathalie Krauth and Ludwig, {Mette Q} and Kathrine Lund{\o} and Urmas Roostalu and Hjort-Gregersen, {Grethe Skovbjerg} and Nielsen, {Duy Anh Gurskov} and Ejdrup, {Aske Lykke} and Pers, {Tune H} and Oksana Dmytriyeva and Jacob Hecksher-Soerensen and Ulrik Gether and Kohlmeier, {Kristi Anne} and Christoffer Clemmensen",
year = "2023",
doi = "10.1016/j.celrep.2023.112466",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity

AU - Falk, Sarah

AU - Petersen, Jonas Odgaard

AU - Svendsen, Charlotte Sashi Aier

AU - Leguizamon, Cesar Ramon Romero

AU - Jørgensen, Søren Heide

AU - Krauth, Nathalie

AU - Ludwig, Mette Q

AU - Lundø, Kathrine

AU - Roostalu, Urmas

AU - Hjort-Gregersen, Grethe Skovbjerg

AU - Nielsen, Duy Anh Gurskov

AU - Ejdrup, Aske Lykke

AU - Pers, Tune H

AU - Dmytriyeva, Oksana

AU - Hecksher-Soerensen, Jacob

AU - Gether, Ulrik

AU - Kohlmeier, Kristi Anne

AU - Clemmensen, Christoffer

PY - 2023

Y1 - 2023

N2 - Glucagon-like peptide-1 receptor (GLP-1R) agonists promote nicotine avoidance. Here, we show that the crosstalk between GLP-1 and nicotine extends beyond effects on nicotine self-administration and can be exploited pharmacologically to amplify the anti-obesity effects of both signals. Accordingly, combined treatment with nicotine and the GLP-1R agonist, liraglutide, inhibits food intake and increases energy expenditure to lower body weight in obese mice. Co-treatment with nicotine and liraglutide gives rise to neuronal activity in multiple brain regions, and we demonstrate that GLP-1R agonism increases excitability of hypothalamic proopiomelanocortin (POMC) neurons and dopaminergic neurons in the ventral tegmental area (VTA). Further, using a genetically encoded dopamine sensor, we reveal that liraglutide suppresses nicotine-induced dopamine release in the nucleus accumbens in freely behaving mice. These data support the pursuit of GLP-1R-based therapies for nicotine dependence and encourage further evaluation of combined treatment with GLP-1R agonists and nicotinic receptor agonists for weight loss.

AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists promote nicotine avoidance. Here, we show that the crosstalk between GLP-1 and nicotine extends beyond effects on nicotine self-administration and can be exploited pharmacologically to amplify the anti-obesity effects of both signals. Accordingly, combined treatment with nicotine and the GLP-1R agonist, liraglutide, inhibits food intake and increases energy expenditure to lower body weight in obese mice. Co-treatment with nicotine and liraglutide gives rise to neuronal activity in multiple brain regions, and we demonstrate that GLP-1R agonism increases excitability of hypothalamic proopiomelanocortin (POMC) neurons and dopaminergic neurons in the ventral tegmental area (VTA). Further, using a genetically encoded dopamine sensor, we reveal that liraglutide suppresses nicotine-induced dopamine release in the nucleus accumbens in freely behaving mice. These data support the pursuit of GLP-1R-based therapies for nicotine dependence and encourage further evaluation of combined treatment with GLP-1R agonists and nicotinic receptor agonists for weight loss.

U2 - 10.1016/j.celrep.2023.112466

DO - 10.1016/j.celrep.2023.112466

M3 - Journal article

C2 - 37148870

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

M1 - 112466

ER -

ID: 346014245