title: The atypical cannabinoid O-1602 stimulates food intake and adiposity in rats.
abstract: OBJECTIVE
  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.
authors: Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S Francisco s/n, Santiago de Compostela (A Coruña), Spain
authors: A
authors: A
authors: Díaz-Arteaga
authors: M J
authors: MJ
authors: Vázquez
authors: R
authors: R
authors: Vazquez-Martínez
authors: M R
authors: MR
authors: Pulido
authors: J
authors: J
authors: Suarez
authors: D A
authors: DA
authors: Velásquez
authors: M
authors: M
authors: López
authors: R A
authors: RA
authors: Ross
authors: F Rodriguez
authors: FR
authors: de Fonseca
authors: F J
authors: FJ
authors: Bermudez-Silva
authors: M M
authors: MM
authors: Malagón
authors: C
authors: C
authors: Diéguez
authors: R
authors: R
authors: Nogueiras
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001835:Body Weight; D002185:Cannabidiol / Q000031:analogs & derivatives; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D043882:Receptors, Cannabinoid / Q000172:deficiency; D012118:Resorcinols / Q000494:pharmacology*
chemical_list: D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D003510:Cyclohexanes; C526692:GPR55 protein, mouse; D043882:Receptors, Cannabinoid; D012118:Resorcinols; D002185:Cannabidiol; C568537:O-1602 compound