The Atypical Cannabinoid O-1602 Stimulates Food Intake And Adiposity In Rats

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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.

Source: The atypical cannabinoid O-1602 stimulat... [Diabetes Obes Metab. 2012] - PubMed - NCBI
 
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