GPR55 is a putative endocannabinoid receptor, which has an affinity for the endogenous cannabinoid ligands anandamide and 2-arachidonyl glycerol, which increases appetite and reduce energy expenditure. O-1602 is an agonist for GPR55/GPR18. There is limited research looking at chronic administration of O-1602 in vivo.
To determine the effect of O-1602 on plasma concentration of hormones involved in appetite and glucose regulation, as well as liver function.
Male Sprague Dawley rats were fed a high fat diet (21% fat) for 9 weeks to induce an obese state, and then administered daily via intraperitoneal (ip) injection for 6 weeks with either 5mg/kg of O-1602 or vehicle, following which rats were anaesthetised and blood was collected via cardiac puncture, into EDTA sample tubes and plasma was stored at -80oC until analysis.
Plasma levels of leptin, ghrelin, GLP-1 and glucagon were analysed using a Bioplex multi-analyte Diabetes Kit. Plasma AST, ALT, GGT and albumin were analysed using a commercially available kit.
Treatment of obese rats for 6 weeks with O-1602, decreased body fat and increased lean tissue mass (%). Food consumption decreased in the first week of the treatment period. There was no difference in body weight, glucose tolerance or the fibrotic marker, collagen, in the liver and heart of O-1602 treated rats compared to obese control.
In addition to a reduction in body fat and food consumption, O-1602 decreased plasma leptin and ghrelin but did not alter GLP-1 or glucagon. This data suggests that O-1602 has a role in regulating adipose storage and appetite. For liver function, AST concentrations were significantly increased in O-1602 treated rats, whereas ALT, GGT and albumin were not altered. Thus this data suggests that despite the weight loss associated with O-1602, further investigation is warranted to determine the whole body effect of treatment with this drug.
Research supported by the Allen Foundation. ACS was supported by Australian Rotary Health Scholarship.