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Published VersionCC BY V4.0, Open Access
Published VersionCC BY V4.0, Open
Journal article
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, Vol.21(16), pp.1-18
2020
PMID: 32824681
Abstract
O-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. C(2)C(12)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 C(2)C(12)myotubes, while APPL2 mRNA was up-regulated in white gastrocnemius in DIO rats treated with O-1918. In C(2)C(12)myotubes treated with O-1918, PGC1 alpha, 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 C(2)C(12)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.
Details
- Title
- The Role of Atypical Cannabinoid Ligands O-1602 and O-1918 on Skeletal Muscle Homeostasis with a Focus on Obesity
- Authors
- Anna C. Simcocks (Author) - Victoria UniversityLannie O'Keefe (Author) - Victoria UniversityKayte A. Jenkin (Author) - Victoria UniversityLauren M. Cornall (Author) - Victoria UniversityEsther Grinfeld (Author) - Victoria UniversityMichael L. Mathai (Author) - Florey Institute of Neuroscience and Mental HealthDeanne H. Hryciw (Author) - Griffith UniversityAndrew J. McAinch (Corresponding Author) - Australian Institute for Musculoskeletal Science
- Publication details
- International Journal of Molecular Sciences, Vol.21(16), pp.1-18
- Publisher
- MDPI AG
- Date published
- 2020
- DOI
- 10.3390/ijms21165922
- ISSN
- 1422-0067; 1661-6596
- PMID
- 32824681
- Copyright note
- ©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/).
- Grant note
- This research was funded by the Allen Foundation (D.H.H., A.J.M.). A.C.S. was supported by Australian Rotary Health and the Rotary Club of Ballarat South PhD scholarship and L.O. and K.A.J. were supported by an Australian Postgraduate Award for their PhD.
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991187227102621
- Output Type
- Journal article
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