期刊
DIABETES OBESITY & METABOLISM
卷 14, 期 3, 页码 234-243出版社
WILEY
DOI: 10.1111/j.1463-1326.2011.01515.x
关键词
adipose tissue; appetite control; body composition; cannabinoids
资金
- Ministerio de Ciencia e Innovacion [BFU2007-60180, BFU2010-17116, BFU2008-02001, RYC-2008-02219, SAF2009-07049, RyC-2007-00211]
- Xunta de Galicia [10PXIB208164PR, PGIDIT06PXIB208063PR, 2010/14]
- Fondo Investigaciones Sanitarias [PS09/01880, PI10/02308, 07/1226]
- Consejeria de Salud de la Junta de Andalucia [PI-0232/2008, CVI-1038, P07-CTS-03039]
- European Union [Health-F2-2008-223713: 'Reprobesity']
- National System of Health (Instituto de Salud Carlos III) [CP07/00283]
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 amphetamineregulated 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.
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