Poster Presentation ANZOS-Breakthrough Discoveries Joint Annual Scientific Meeting 2018

The effect of atypical cannabinoid compounds on skeletal muscle homeostasis in a diet induced obese rat model. (#245)

Anna C Simcocks 1 , Lannie O'Keefe 1 2 , Kayte A Jenkin 3 , Michael L Mathai 1 , Deanne H Hryciw 4 , Andrew J McAinch 1
  1. Institute for Health & Sport, Victoria University, St Albans, VIC, Australia
  2. First Year College, Victoria University, Footscray, VIC, Australia
  3. School of Science and Health, Western Sydney University, Campbell Town, VIC, Australia
  4. School of Environment and Sciences, Griffith University, Nathan, Queensland, Australia

Introduction:

Atypical cannabinoid ligands O-1602 and O-1918 have an affinity to putative cannabinoid receptors including GPR18. The endocannbinoid system is involved in regulating energy homeostasis in obesity and skeletal muscle metabolism. Currently the expression of GPR18 in skeletal muscle and the effect that atypical cannabinoids have on skeletal muscle homeostasis is unclear.

Aim:

To determine whether GPR18 is expressed in skeletal muscle in diet induced obesity (DIO) and if the receptor’s expression is altered by treatment with atypical cannabinoids. To determine the effect of atypical cannabinoids on mRNA expression of markers involved in skeletal muscle homeostasis in red (RG) or white gastrocnemius (WG) in DIO.

Methodology:

Male Sprague Dawley rats were fed a high fat diet (41% energy from fat) for 9weeks to induce obesity. DIO rats were treated with 1mg/kg-O-1918, 5mg/kg-O-1602 or vehicle for 6weeks. Rats were deeply anaesthetised, RG and WG were collected and snap frozen, then rats were administered sodium pentabarbitone. mRNA expression of markers of adiponectin signalling, oxidative capacity and fatty acid oxidation were determined.

Results/ Discussion/ Conclusion:

In DIO rats, GPR18 mRNA was expressed in gastrocnemius muscle and expression was higher in RG compared to WG. Treatment with atypical cannabinoids did not alter GPR18 expression. The development of more selective ligands for GPR18 to pharmacologically target this receptor in skeletal muscle may be beneficial for obesity.

In DIO, O-1602 did not alter markers of energy homeostasis in RG or WG and may not be a beneficial obesity pharmacological target in skeletal muscle. O-1918 altered some markers of skeletal muscle metabolism in a fibre type-specific fashion. Further investigation into O-1918-treated skeletal muscle tissue is required.

Acknowledgements:

Supported by the Allen Foundation, ACS supported by Australian Rotary Health and Rotary Club of Ballarat South, LO’K and KAJ were supported by Australian Postgraduate Scholarship.