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dc.contributor.authorSimcocks, Anna C
dc.contributor.authorO’Keefe, Lannie
dc.contributor.authorJenkin, Kayte A
dc.contributor.authorCornall, Lauren M
dc.contributor.authorGrinfeld, Esther
dc.contributor.authorMathai, Michael L
dc.contributor.authorHryciw, Deanne H
dc.contributor.authorMcAinch, Andrew J
dc.date.accessioned2020-08-21T04:30:21Z
dc.date.available2020-08-21T04:30:21Z
dc.date.issued2020
dc.identifier.issn1422-0067
dc.identifier.doi10.3390/ijms21165922
dc.identifier.urihttp://hdl.handle.net/10072/396641
dc.description.abstractO-1602 and O-1918 are atypical cannabinoid ligands for GPR55 and GPR18, which may be novel pharmaceuticals for the treatment of obesity by targeting energy homeostasis regulation in skeletal muscle. This study aimed to determine the effect of O-1602 or O-1918 on markers of oxidative capacity and fatty acid metabolism in the skeletal muscle. Diet-induced obese (DIO) male Sprague Dawley rats were administered a daily intraperitoneal injection of O-1602, O-1918 or vehicle for 6 weeks. C2C12 myotubes were treated with O-1602 or O-1918 and human primary myotubes were treated with O-1918. GPR18 mRNA was expressed in the skeletal muscle of DIO rats and was up-regulated in red gastrocnemius when compared with white gastrocnemius. O-1602 had no effect on mRNA expression on selected markers for oxidative capacity, fatty acid metabolism or adiponectin signalling in gastrocnemius from DIO rats or in C2C12 myotubes, while APPL2 mRNA was up-regulated in white gastrocnemius in DIO rats treated with O-1918. In C2C12 myotubes treated with O-1918, PGC1α, NFATc1 and PDK4 mRNA were up-regulated. There were no effects of O-1918 on mRNA expression in human primary myotubes derived from obese and obese T2DM individuals. In conclusion, O-1602 does not alter mRNA expression of key pathways important for skeletal muscle energy homeostasis in obesity. In contrast, O-1918 appears to alter markers of oxidative capacity and fatty acid metabolism in C2C12 myotubes only. GPR18 is expressed in DIO rat skeletal muscle and future work could focus on selectively modulating GPR18 in a tissue-specific manner, which may be beneficial for obesity-targeted therapies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherMDPI AG
dc.relation.ispartofpagefrom5922
dc.relation.ispartofissue16
dc.relation.ispartofjournalInternational Journal of Molecular Sciences
dc.relation.ispartofvolume21
dc.subject.fieldofresearchOther chemical sciences
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchOther biological sciences
dc.subject.fieldofresearchcode3499
dc.subject.fieldofresearchcode3105
dc.subject.fieldofresearchcode3199
dc.titleThe Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationSimcocks, AC; O’Keefe, L; Jenkin, KA; Cornall, LM; Grinfeld, E; Mathai, ML; Hryciw, DH; McAinch, AJ, The Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity, International Journal of Molecular Sciences, 21 (16), pp. 5922
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-08-21T03:48:54Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorSkelly, Deanne


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