Article ; Online: GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity.
2023 Volume 42, Issue 5, Page(s) 112466
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- ... ...
| 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. |
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| MeSH term(s) | Mice ; Animals ; Glucagon-Like Peptide 1/pharmacology ; Liraglutide/pharmacology ; Nicotine/pharmacology ; Dopamine ; Obesity/drug therapy ; Obesity/metabolism |
| Chemical Substances | Glucagon-Like Peptide 1 (89750-14-1) ; Liraglutide (839I73S42A) ; Nicotine (6M3C89ZY6R) ; Dopamine (VTD58H1Z2X) |
| Language | English |
| Publishing date | 2023-05-05 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649101-1 |
| ISSN | 2211-1247 ; 2211-1247 |
| ISSN (online) | 2211-1247 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2023.112466 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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