The atypical cannabinoid O-1602 stimulates food intake and adiposity in rats.

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.

• Authors: A Díaz-Arteaga, M J Vázquez, R Vazquez-Martínez, M R Pulido, J Suarez, D A Velásquez, M López, R A Ross, F Rodriguez de Fonseca, F J Bermudez-Silva, M M Malagón, C Diéguez, R Nogueiras
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 14 Issue 3 Pg. 234-43 (Mar 2012) ISSN: 1463-1326 [Electronic] England
• PMID: 21981246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Cannabinoid Receptor Agonists
• Cannabinoids
• Cyclohexanes
• GPR55 protein, mouse
• Receptors, Cannabinoid
• Resorcinols
• Cannabidiol
• O-1602 compound

Topics

• Adipocytes (metabolism)
• Adiposity (drug effects)
• Animals
• Body Weight
• Cannabidiol (analogs & derivatives)
• Cannabinoid Receptor Agonists
• Cannabinoids (pharmacology)
• Cyclohexanes (pharmacology)
• Eating (drug effects)
• Energy Metabolism
• Male
• Mice
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Receptors, Cannabinoid (deficiency)
• Resorcinols (pharmacology)