Publication:
The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice.

dc.contributor.authorRomero-Zerbo, Silvana Y
dc.contributor.authorRuz-Maldonado, Inmaculada
dc.contributor.authorEspinosa-Jimenez, Vanesa
dc.contributor.authorRafacho, Alex
dc.contributor.authorGomez-Conde, Ana I
dc.contributor.authorSanchez-Salido, Lourdes
dc.contributor.authorCobo-Vuilleumier, Nadia
dc.contributor.authorGauthier, Benoit R
dc.contributor.authorTinahones, Francisco J
dc.contributor.authorPersaud, Shanta J
dc.contributor.authorBermudez-Silva, Francisco J
dc.contributor.funderConsejería de Salud de la Junta de Andalucía, “Andalucía se mueve con Europa”
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderMinisterio de Sanidad, Gobierno de España
dc.date.accessioned2023-01-25T09:47:52Z
dc.date.available2023-01-25T09:47:52Z
dc.date.issued2017-06-21
dc.description.abstractLH-21 is a triazol derivative that has been described as a low-permeant neutral CB1 antagonist, though its pharmacology is still unclear. It has been associated with anti-obesity actions in obese rats. However, its role in preventing type 2 diabetes (T2D) onset have not been studied yet. Given CB1 receptors remain as potential pharmacological targets to fight against obesity and T2D, we wanted to explore the metabolic impact of this compound in an animal model of obesity and pre-diabetes as well as the lack of relevant actions in related central processes such as anxiety. C57BL/6J mice were rendered obese and pre-diabetic by feeding a high-fat diet for 15 weeks and then treated with LH-21 or vehicle for two weeks. Food intake, body weight and glucose handling were assessed, together with other relevant parameters. Behavioural performance was evaluated by the open field test and the elevated plus maze. LH-21 did not affect food intake nor body weight but it improved glucose handling, displaying tissue-specific beneficial actions. Unexpectedly, LH-21 induced anxiolysis and reverted obesity-induced anxiety, apparently through GPR55 receptor. These results suggest that LH-21 can be a new candidate to fight against diabetes onset. Indeed, this compound shows potential in counteracting obesity-related anxiety.
dc.description.sponsorshipThis work was supported by Consejería de Salud de la Junta de Andalucía, “Andalucía se mueve con Europa” (PI0574-2012 to S.Y.R.Z.) and Instituto de Salud Carlos III (ISCIII, co-funded by FEDER, EU, “Una manera de hacer Europa”), Ministerio de Sanidad, Gobierno de España (PI13/00309 to F.J.B.S. and PI13/00593 to B.R.G.). S.Y.R.Z. is recipient of a postdoctoral fellowship from Consejeria de Salud de la Junta de Andalucia (RH-0070-2013). I.R.M. is recipient of PFIS predoctoral fellowships from ISCIII (FI11/00636). A.R. received a short-term stay fellowship from Banco Santander (Programa Bolsas Iberoamericanas Jovens Professores e Pesquisadores). FJBS is recipient of a “Miguel Servet II” research contract (CPII13/00042) and also belongs to the regional “Nicolás Monardes” research program of the Consejería de Salud (C-0070-2012; Junta de Andalucía, Spain). CIBERDEM is an initiative of the Instituto de Salud Carlos III. Grupo de trabajo de islotes pancreáticos, Sociedad Española de Diabetes (SED).
dc.description.versionSi
dc.identifier.citationRomero-Zerbo SY, Ruz-Maldonado I, Espinosa-Jiménez V, Rafacho A, Gómez-Conde AI, Sánchez-Salido L, et al. The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice. Sci Rep. 2017 Jun 21;7(1):3946
dc.identifier.doi10.1038/s41598-017-03292-w
dc.identifier.essn2045-2322
dc.identifier.pmcPMC5479807
dc.identifier.pmid28638091
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479807/pdf
dc.identifier.unpaywallURLhttps://www.nature.com/articles/s41598-017-03292-w.pdf
dc.identifier.urihttp://hdl.handle.net/10668/11331
dc.issue.number1
dc.journal.titleScientific reports
dc.journal.titleabbreviationSci Rep
dc.language.isoen
dc.organizationInstituto de Investigación Biomédica de Málaga-IBIMA
dc.organizationHospital Universitario Regional de Málaga
dc.organizationCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER
dc.page.number13
dc.provenanceRealizada la curación de contenido 15/05/2025
dc.publisherNature Publishing Group
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDPI0574-2012
dc.relation.projectIDPI13/00309
dc.relation.projectIDPI13/00593
dc.relation.projectIDRH-0070-2013
dc.relation.projectIDC-0070-2012
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-017-03292-w
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectInflammation Mediators
dc.subjectInsulin
dc.subjectIslets of Langerhans
dc.subjectLiver
dc.subjectObesity
dc.subject.decsObesidad
dc.subject.decsAnsiedad
dc.subject.decsPeso corporal
dc.subject.decsGlucosa
dc.subject.decsDiabetes Mellitus tipo 2
dc.subject.decsPrueba de campo abierto
dc.subject.meshAnimals
dc.subject.meshAnxiety
dc.subject.meshBehavior, Animal
dc.subject.meshBlood Glucose
dc.subject.meshDiet, High-Fat
dc.subject.meshDisease Models, Animal
dc.subject.meshMice, Inbred C57BL
dc.subject.meshPrediabetic State
dc.subject.meshReceptor, Cannabinoid, CB1
dc.subject.meshTriazoles
dc.titleThe cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number7
dspace.entity.typePublication

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