Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons drives overconsumption of palatable food and obesity.


Journal

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907

Informations de publication

Date de publication:
04 2021
Historique:
received: 05 05 2020
accepted: 29 12 2020
revised: 23 12 2020
pubmed: 10 2 2021
medline: 24 6 2021
entrez: 9 2 2021
Statut: ppublish

Résumé

Palatable food can promote overfeeding beyond homeostatic requirements, thereby constituting a major risk to obesity. Here, the lack of cannabinoid type 1 receptor (CB1) in dorsal telencephalic glutamatergic neurons (Glu-CB1-KO) abrogated the overconsumption of palatable food and the development of obesity. On low-fat diet, no genotype differences were observed. However, under palatable food conditions, Glu-CB1-KO mice showed decreased body weight and food intake. Notably, Glu-CB1-KO mice were protected from alterations in the reward system after high-fat diet feeding. Interestingly, obese wild-type mice showed a superior olfactory detection as compared to mutant mice, suggesting a link between overconsumption of palatable food and olfactory function. Reconstitution of CB1 expression in olfactory cortex in high-fat diet-fed Glu-CB1-KO mice using viral gene delivery partially reversed the lean phenotype concomitantly with improved odor perception. These findings indicate that CB1 in cortical glutamatergic neurons regulates hedonic feeding, whereby a critical role of the olfactory cortex was uncovered as an underlying mechanism.

Identifiants

pubmed: 33558679
doi: 10.1038/s41386-021-00957-z
pii: 10.1038/s41386-021-00957-z
pmc: PMC8105345
doi:

Substances chimiques

Cannabinoids 0
Receptor, Cannabinoid, CB1 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

982-991

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Auteurs

Inigo Ruiz de Azua (I)

Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. inigo.azua@lir-mainz.de.
Leibniz Institute for Resilience Research (LIR), Mainz, Germany. inigo.azua@lir-mainz.de.

Elena Martin-Garcia (E)

Laboratory of Neuropharmacology-Neurophar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Laura Domingo-Rodriguez (L)

Laboratory of Neuropharmacology-Neurophar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Alejandro Aparisi Rey (A)

Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Diego Pascual Cuadrado (D)

Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Larglinda Islami (L)

Leibniz Institute for Resilience Research (LIR), Mainz, Germany.

Petri Turunen (P)

Microscopy Core Facility, Institute of Molecular Biology (IMB), Mainz, Germany.

Floortje Remmers (F)

Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Beat Lutz (B)

Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Leibniz Institute for Resilience Research (LIR), Mainz, Germany.

Rafael Maldonado (R)

Laboratory of Neuropharmacology-Neurophar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.

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