{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:05:09Z","timestamp":1760551509241,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2017-84117-R and PID2020-113430RB-I00"],"award-info":[{"award-number":["SAF2017-84117-R and PID2020-113430RB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010473","name":"Alzheimer's Foundation of America","doi-asserted-by":"publisher","award":["AARFD-17-503612"],"award-info":[{"award-number":["AARFD-17-503612"]}],"id":[{"id":"10.13039\/100010473","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cannabinoids have been reported as orexigenic, i.e., as promoting food intake that, among others, is controlled by the so-called \u201chunger\u201d 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.<\/jats:p>","DOI":"10.3390\/ijms22168928","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:58:06Z","timestamp":1629367086000},"page":"8928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["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"],"prefix":"10.3390","volume":"22","author":[{"given":"Jaume","family":"Lillo","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos III, Valderrebollo, 5, 28031 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Lillo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Zafra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0472-3754","authenticated-orcid":false,"given":"Cristina","family":"Miralpeix","sequence":"additional","affiliation":[{"name":"Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08190 Sant Cugat del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-6819","authenticated-orcid":false,"given":"Rafael","family":"Rivas-Santisteban","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos III, Valderrebollo, 5, 28031 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-4300","authenticated-orcid":false,"given":"N\u00faria","family":"Casals","sequence":"additional","affiliation":[{"name":"Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08190 Sant Cugat del Vall\u00e8s, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, Monforte de Lemos, 3, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-0873","authenticated-orcid":false,"given":"Gemma","family":"Navarro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos III, Valderrebollo, 5, 28031 Madrid, Spain"},{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona (UBNeuro), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-4919","authenticated-orcid":false,"given":"Rafael","family":"Franco","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CiberNed), National Institute of Health Carlos III, Valderrebollo, 5, 28031 Madrid, Spain"},{"name":"Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, 08028 Barcelona, Spain"},{"name":"School of Chemistry, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104801","DOI":"10.1016\/j.phrs.2020.104801","article-title":"Pharmacological potential of varinic-, minor-, and acidic phytocannabinoids","volume":"158","author":"Franco","year":"2020","journal-title":"Pharmacol. 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