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Journal article
Anti-obesity effect of the CB2 receptor agonist JWH-015 in diet-induced obese mice
PLoS One, Vol.10(11), pp.1-19
2015
PMID: 26588700
Abstract
The cannabinoid receptor 2 (CB2) is well known for its immune modulatory role. However, recent localisation of CB2 receptors in metabolically active tissue suggests that the CB2 receptor plays a significant role in energy homeostasis. This study was designed to investigate the impact of chronic CB2 receptor stimulation on food intake, body weight and mood. Lean male C57BL/6 mice were injected i.p. with the selective CB2 receptor agonist, JWH-015 (0.0, 1.0, 5.0 and 10.0 mg kg-1) to establish dose response parameters. Mice made obese following exposure to a diet consisting of 19.4 MJ/kg (4641 Kcal/kg) of energy (19.0% protein, 21.0% total fat, 4.7% crude fiber, and 4.7% AD fiber were given either vehicle or 10 mg/kg JWH-015. Impact on mood, food intake, body weight, plasma metabolites, expression of key metabolic proteins in the brown adipose tissue (BAT) and white adipose tissue (WAT), and markers of inflammation were measured. High dose (10 mg/kg) JWH-015 reduced food intake after 1, 2, 4, and 24 h in lean mice. When given to diet induced obese (DIO) mice, a 10 mg/kg dose of JWH-015 significantly reduced body weight compared to vehicle. This dose led to a shift in markers of lipid metabolism and inflammation in WAT consistent with lipolysis and improved immune response. Furthermore, JWH-015 (10 mg/kg) produced a transient reduction in food intake and significant reduction in fat mass and adipocyte cell size. Importantly, JWH-015 produced an anxiolytic response in the elevated plus maze while having no effect on immobility time in the forced swim test. It should be noted that though the 10 mg/kg dose produced positive effects on the obese state, the possibility that these effects are mediated via non-CB2 receptor mechanisms cannot be ruled out. These results demonstrate a role for CB2 receptors in modulating energy homeostasis and obesity associated metabolic pathologies in the absence of any adverse impact on mood.
Details
- Title
- Anti-obesity effect of the CB2 receptor agonist JWH-015 in diet-induced obese mice
- Authors
- A. N.A. Verty - Monash UniversityA. Stefanidis - Monash UniversityA. J. McAinch - Victoria UniversityD. H. Hryciw - The University of MelbourneBrian Oldfield (Corresponding Author) - Monash University
- Publication details
- PLoS One, Vol.10(11), pp.1-19
- Publisher
- Public Library of Science
- Date published
- 2015
- DOI
- 10.1371/journal.pone.0140592
- ISSN
- 1932-6203
- PMID
- 26588700
- Copyright note
- © 2015 Verty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
- Grant note
- BJO was the recipient of a National Health and Medical Research Council (NHMRC) Principle Research Fellowship. ANAV was the recipient of a NHMRC Peter Doherty Postdoctoral Research Fellowship during the conduct of these studies. ANAV is currently a Research Fellow at the Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University. AJM was supported through the Australian Government’s Collaborative Research Networks (CRN) program.
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991187227602621
- Output Type
- Journal article
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