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dc.contributor.authorSimcocks, Anna C
dc.contributor.authorJenkin, Kayte A
dc.contributor.authorO'Keefe, Lannie
dc.contributor.authorSamuel, Chrishan S
dc.contributor.authorMathai, Michael L
dc.contributor.authorMcAinch, Andrew J
dc.contributor.authorHryciw, Deanne H
dc.date.accessioned2019-06-19T13:07:23Z
dc.date.available2019-06-19T13:07:23Z
dc.date.issued2019
dc.identifier.issn2049-3614
dc.identifier.doi10.1530/EC-18-0535
dc.identifier.urihttp://hdl.handle.net/10072/385105
dc.description.abstractAtypical 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBIOSCIENTIFICA LTD
dc.relation.ispartofpagefrom203
dc.relation.ispartofpageto216
dc.relation.ispartofissue3
dc.relation.ispartofjournalENDOCRINE CONNECTIONS
dc.relation.ispartofvolume8
dc.subject.fieldofresearchNutrition and dietetics
dc.subject.fieldofresearchcode3210
dc.titleAtypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 The authors. This work is licensed under a Creative Commons Attribution 4.0 International License.
gro.hasfulltextFull Text
gro.griffith.authorSkelly, Deanne


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