Artículo
The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice
Autor/es | Romero Zerbo, Silvana Y.
Ruz Maldonado, Inmaculada Espinosa Jiménez, Vanesa Cobo Vuilleumier, Nadia Gauthier, Benoit R. |
Fecha de publicación | 2017 |
Fecha de depósito | 2017-08-16 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Ministerio de Sanidad. España Junta de Andalucía |
Identificador del proyecto | 13/00309 to F.J.B.S. and PI13/00593 to B.R.G
C-0070-2012; |
Cita | Romero Zerbo, S.Y., Ruz Maldonado, I., Espinosa Jiménez, V., Cobo Vuilleumier, N. y Gauthier, B.R. (2017). The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice. Scientific Reports, 7 (3946) |
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