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- Title
The atypical cannabinoid O-1602 stimulates food intake and adiposity in rats.
- Authors
Díaz-Arteaga, A.; Vázquez, M. J.; Vazquez-Martínez, R.; Pulido, M. R.; Suarez, J.; Velásquez, D. A.; López, M.; Ross, R. A.; de Fonseca, F. Rodriguez; Bermudez-Silva, F. J.; Malagón, M. M.; Diéguez, C.; Nogueiras, R.
- Abstract
Aims: Cannabinoids are known to control energy homeostasis. Atypical cannabinoids produce pharmacological effects via unidentified targets. We sought to investigate whether the atypical cannabinoid O-1602 controls food intake and body weight. Methods: The rats were injected acutely or subchronically with O-1602, and the expression of several factors involved in adipocyte metabolism was assessed by real-time polymerase chain reaction. In vivo findings were corroborated with in vitro studies incubating 3T3-L1 adipocytes with O-1602, and measuring intracellular calcium and lipid accumulation. Finally, as some reports suggest that O-1602 is an agonist of the putative cannabinoid receptor GPR55, we tested it in mice lacking GPR55. Results: Central and peripheral administration of O-1602 acutely stimulates food intake, and chronically increases adiposity. The hyperphagic action of O-1602 is mediated by the downregulation of mRNA and protein levels of the anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript. The effects on fat mass are independent of food intake, and involve a decrease in the expression of lipolytic enzymes such as hormone sensitive lipase and adipose triglyceride lipase in white adipose tissue. Consistently, in vitro data showed that O-1602 increased the levels of intracellular calcium and lipid accumulation in adipocytes. Finally, we injected O-1602 in GPR55 −/− mice and found that O-1602 was able to induce feeding behaviour in GPR55-deficient mice. Conclusions: These findings show that O-1602 modulates food intake and adiposity independently of GPR55 receptor. Thus atypical cannabinoids may represent a novel class of molecules involved in energy balance.
- Subjects
CANNABINOIDS; TERPENES; CANNABIS (Genus); FAT cells; LIPASES
- Publication
Diabetes, Obesity & Metabolism, 2012, Vol 14, Issue 3, p234
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/j.1463-1326.2011.01515.x