RT Journal Article
T1 The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice.
A1 Romero-Zerbo, Silvana Y
A1 Ruz-Maldonado, Inmaculada
A1 Espinosa-Jimenez, Vanesa
A1 Rafacho, Alex
A1 Gomez-Conde, Ana I
A1 Sanchez-Salido, Lourdes
A1 Cobo-Vuilleumier, Nadia
A1 Gauthier, Benoit R
A1 Tinahones, Francisco J
A1 Persaud, Shanta J
A1 Bermudez-Silva, Francisco J
K1 Inflammation Mediators
K1 Insulin
K1 Islets of Langerhans
K1 Liver
K1 Obesity
AB 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.
PB Nature Publishing Group
YR 2017
FD 2017-06-21
LK http://hdl.handle.net/10668/11331
UL http://hdl.handle.net/10668/11331
LA en
NO Romero-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
NO This 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).
DS RISalud
RD Aug 17, 2025