title: Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation.
abstract: The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours.
authors.affiliation: Discovery Sciences Transgenics, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Mikael
authors.identifier: http://orcid.org/0000-0002-4654-7701
authors.initials: M
authors.lastname: Bjursell
authors.affiliation: Cardiovascular and Metabolic diseases (CVMD) Innovative Medicines and early Development Biotech Unit, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Ryberg
authors.affiliation: Discovery Sciences Transgenics, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: CVMD Translational Medicine Unit, Early Clinical Development AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Greasley
authors.affiliation: Discovery Sciences Transgenics, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.affiliation: Dept. of Molecular & Clinical Medicine, Inst. of Medicine, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hjorth
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature; D002151:Calorimetry; D063387:Cannabinoid Receptor Antagonists / Q000378:metabolism; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D017353:Gene Deletion; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism; D011720:Pyrazoles / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D013697:Thermosensing / Q000235:genetics
chemical_list: D063387:Cannabinoid Receptor Antagonists; C526692:GPR55 protein, mouse; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000077285:Rimonabant