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Sci Rep. 2017 Jun 21;7(1):3946. doi: 10.1038/s41598-017-03292-w.

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

Author information

1
Unidad de Gestión Clínica Intercentros de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. yanina.romero@ibima.eu.
2
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Málaga, Spain. yanina.romero@ibima.eu.
3
Unidad de Gestión Clínica Intercentros de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
4
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Málaga, Spain.
5
Diabetes Research Group, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London, SE1 1UL, UK.
6
Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900, Florianópolis, SC, Brazil.
7
Bioimaging facility, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
8
Stem Cells Department, Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, Spain.
9
Centro de Investigación Biomédica en Red de Obesidad y Nutrición (CIBEROBN), Málaga, Spain.
10
Unidad de Gestión Clínica Intercentros de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. javier.bermudez@ibima.eu.
11
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Málaga, Spain. javier.bermudez@ibima.eu.

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.

PMID:
28638091
PMCID:
PMC5479807
DOI:
10.1038/s41598-017-03292-w
[Indexed for MEDLINE]
Free PMC Article

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