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

Abstract LH-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. Gi...

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Autores principales:	Silvana Y. Romero-Zerbo, Inmaculada Ruz-Maldonado, Vanesa Espinosa-Jiménez, Alex Rafacho, Ana I. Gómez-Conde, Lourdes Sánchez-Salido, Nadia Cobo-Vuilleumier, Benoit R. Gauthier, Francisco J. Tinahones, Shanta J. Persaud, Francisco J. Bermúdez-Silva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37b7287839a5497faf990573a8d0dd27
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spelling	oai:doaj.org-article:37b7287839a5497faf990573a8d0dd272021-12-02T12:32:04ZThe cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice10.1038/s41598-017-03292-w2045-2322https://doaj.org/article/37b7287839a5497faf990573a8d0dd272017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03292-whttps://doaj.org/toc/2045-2322Abstract LH-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.Silvana Y. Romero-ZerboInmaculada Ruz-MaldonadoVanesa Espinosa-JiménezAlex RafachoAna I. Gómez-CondeLourdes Sánchez-SalidoNadia Cobo-VuilleumierBenoit R. GauthierFrancisco J. TinahonesShanta J. PersaudFrancisco J. Bermúdez-SilvaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silvana Y. Romero-Zerbo Inmaculada Ruz-Maldonado Vanesa Espinosa-Jiménez Alex Rafacho Ana I. Gómez-Conde Lourdes Sánchez-Salido Nadia Cobo-Vuilleumier Benoit R. Gauthier Francisco J. Tinahones Shanta J. Persaud Francisco J. Bermúdez-Silva The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
description	Abstract LH-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.
format	article
author	Silvana Y. Romero-Zerbo Inmaculada Ruz-Maldonado Vanesa Espinosa-Jiménez Alex Rafacho Ana I. Gómez-Conde Lourdes Sánchez-Salido Nadia Cobo-Vuilleumier Benoit R. Gauthier Francisco J. Tinahones Shanta J. Persaud Francisco J. Bermúdez-Silva
author_facet	Silvana Y. Romero-Zerbo Inmaculada Ruz-Maldonado Vanesa Espinosa-Jiménez Alex Rafacho Ana I. Gómez-Conde Lourdes Sánchez-Salido Nadia Cobo-Vuilleumier Benoit R. Gauthier Francisco J. Tinahones Shanta J. Persaud Francisco J. Bermúdez-Silva
author_sort	Silvana Y. Romero-Zerbo
title	The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
title_short	The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
title_full	The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
title_fullStr	The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
title_full_unstemmed	The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
title_sort	cannabinoid ligand lh-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/37b7287839a5497faf990573a8d0dd27
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The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice

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