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Identification of the Ghrelin and Cannabinoid CB2 Receptor Heteromer Functionality and Marked Upregulation in Striatal Neurons from Offspring of Mice under a High-Fat Diet

1
Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos III, Valderrebollo, 5, 28031 Madrid, Spain
2
Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, 08028 Barcelona, Spain
3
Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain
4
Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08190 Sant Cugat del Vallès, Spain
5
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Monforte de Lemos, 3, 28029 Madrid, Spain
6
Institut de Neurociències, Universitat de Barcelona (UBNeuro), 08035 Barcelona, Spain
7
School of Chemistry, University of Barcelona, 08028 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Equally contributed.
Academic Editor: Alessia Ligresti
Int. J. Mol. Sci. 2021, 22(16), 8928; https://doi.org/10.3390/ijms22168928
Received: 1 July 2021 / Revised: 11 August 2021 / Accepted: 13 August 2021 / Published: 19 August 2021
(This article belongs to the Section Bioactives and Nutraceuticals)
Cannabinoids have been reported as orexigenic, i.e., as promoting food intake that, among others, is controlled by the so-called “hunger” hormone, ghrelin. The aim of this paper was to look for functional and/or molecular interactions between ghrelin GHSR1a and cannabinoid CB2 receptors at the central nervous system (CNS) level. In a heterologous system we identified CB2-GHSR1a receptor complexes with a particular heteromer print consisting of impairment of CB2 receptor/Gi-mediated signaling. The blockade was due to allosteric interactions within the heteromeric complex as it was reverted by antagonists of the GHSR1a receptor. Cannabinoids acting on the CB2 receptor did not affect cytosolic increases of calcium ions induced by ghrelin acting on the GHSR1a receptor. In situ proximity ligation imaging assays confirmed the expression of CB2-GHSR1a receptor complexes in both heterologous cells and primary striatal neurons. We tested heteromer expression in neurons from offspring of high-fat-diet mouse mothers as they have more risk to be obese. Interestingly, there was a marked upregulation of those complexes in striatal neurons from siblings of pregnant female mice under a high-fat diet. View Full-Text
Keywords: orexigenic; anorexia; marihuana; phytocannabinoids; G protein-coupled receptors; pharmacology; receptor heteromers; signaling; high-fat diet; obesity orexigenic; anorexia; marihuana; phytocannabinoids; G protein-coupled receptors; pharmacology; receptor heteromers; signaling; high-fat diet; obesity
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MDPI and ACS Style

Lillo, J.; Lillo, A.; Zafra, D.A.; Miralpeix, C.; Rivas-Santisteban, R.; Casals, N.; Navarro, G.; Franco, R. Identification of the Ghrelin and Cannabinoid CB2 Receptor Heteromer Functionality and Marked Upregulation in Striatal Neurons from Offspring of Mice under a High-Fat Diet. Int. J. Mol. Sci. 2021, 22, 8928. https://doi.org/10.3390/ijms22168928

AMA Style

Lillo J, Lillo A, Zafra DA, Miralpeix C, Rivas-Santisteban R, Casals N, Navarro G, Franco R. Identification of the Ghrelin and Cannabinoid CB2 Receptor Heteromer Functionality and Marked Upregulation in Striatal Neurons from Offspring of Mice under a High-Fat Diet. International Journal of Molecular Sciences. 2021; 22(16):8928. https://doi.org/10.3390/ijms22168928

Chicago/Turabian Style

Lillo, Jaume, Alejandro Lillo, David A. Zafra, Cristina Miralpeix, Rafael Rivas-Santisteban, Núria Casals, Gemma Navarro, and Rafael Franco. 2021. "Identification of the Ghrelin and Cannabinoid CB2 Receptor Heteromer Functionality and Marked Upregulation in Striatal Neurons from Offspring of Mice under a High-Fat Diet" International Journal of Molecular Sciences 22, no. 16: 8928. https://doi.org/10.3390/ijms22168928

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