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  • Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity

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    Author(s)
    Simcocks, Anna C
    Jenkin, Kayte A
    O'Keefe, Lannie
    Samuel, Chrishan S
    Mathai, Michael L
    McAinch, Andrew J
    Hryciw, Deanne H
    Griffith University Author(s)
    Skelly, Deanne
    Year published
    2019
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    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 ...
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    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-1α, IL-2, IL-17α, 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.
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    Journal Title
    ENDOCRINE CONNECTIONS
    Volume
    8
    Issue
    3
    DOI
    https://doi.org/10.1530/EC-18-0535
    Copyright Statement
    © 2019 The authors. This work is licensed under a Creative Commons Attribution 4.0 International License.
    Subject
    Nutrition and dietetics
    Publication URI
    http://hdl.handle.net/10072/385105
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    • Journal articles

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