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Journal article
Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity
Endocrine Connections, Vol.8(3), pp.203-216
2019
PMID: 30707678
Abstract
Atypical cannabinoid compounds O-1602 and O-1918 are ligands for the putative cannabinoid receptors G protein-coupled receptor 55 and G protein-coupled receptor 18. The role of O-1602 and O-1918 in attenuating obesity and obesity-related pathologies is unknown. Therefore, we aimed to determine the role that either compound had on body weight and body composition, renal and hepatic function in diet-induced obesity. Male Sprague-Dawley rats were fed a high-fat diet (40% digestible energy from lipids) or a standard chow diet for 10 weeks. In a separate cohort, male Sprague-Dawley rats were fed a high-fat diet for 9 weeks and then injected daily with 5 mg/kg O-1602, 1 mg/kg O-1918 or vehicle (0.9% saline/0.75% Tween 80) for a further 6 weeks. Our data demonstrated that high-fat feeding upregulates whole kidney G protein receptor 55 expression. In diet-induced obesity, we also demonstrated O-1602 reduces body weight, body fat and improves albuminuria. Despite this, treatment with O-1602 resulted in gross morphological changes in the liver and kidney. Treatment with O-1918 improved albuminuria, but did not alter body weight or fat composition. In addition, treatment with O-1918 also upregulated circulation of pro-inflammatory cytokines including IL-1 alpha, IL-2, IL-17 alpha, IL-18 and RANTES as well as plasma AST. Thus O-1602 and O-1918 appear not to be suitable treatments for obesity and related comorbidities, due to their effects on organ morphology and pro-inflammatory signaling in obesity.
Details
- Title
- Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity
- Authors
- Anna C. Simcocks - Victoria UniversityKayte A. Jenkin - Victoria UniversityLannie O'Keefe - Victoria UniversityChrishan S. Samuel - Monash UniversityMichael L. Mathai - Florey Institute of Neuroscience and Mental HealthAndrew J. McAinch - Australian Institute for Musculoskeletal ScienceDeanne H. Hryciw (Corresponding Author) - Griffith University
- Publication details
- Endocrine Connections, Vol.8(3), pp.203-216
- Publisher
- BioScientifica Ltd.
- Date published
- 2019
- DOI
- 10.1530/EC-18-0535
- ISSN
- 2049-3614
- PMID
- 30707678
- Copyright note
- This work is licensed under a Creative Commons Attribution 4.0 International License.
- Grant note
- This work was supported by the Allen Foundation (D H H, A J M), and through the Australian Government’s Collaborative Research Networks (CRN) program (A J M). Scholarship funding by Australian Postgraduate Award (K A J, L O) and Australian Rotary Health and the Rotary Club of Ballarat South (A C S).
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991187227002621
- Output Type
- Journal article
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