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
Zafra, David A.
Miralpeix Monclús, Cristina
Casals i Farré, Núria
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.
61 - Medicina
Receptors acoblats a proteïnes G
Dieta rica en greixos
Receptores acoplados a proteína G
Dieta alta en grasas
G protein-coupled receptors
Is part of
International Journal of Molecular Sciences
Lillo, Jaume; Lillo, Alejandro; Zafra, David A. [et al.]. 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. Disponible en: <https://www.mdpi.com/1422-0067/22/16/8928>. Fecha de acceso: 20 sep. 2021. DOI: 10.3390/ijms22168928
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- Ciències de la Salut 
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