Role of the endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons |
| |
| Authors: | L H V?h?talo S T Ruohonen S M?kel? L Ailanen A-M Penttinen T Stormi T Kauko F Piscitelli C Silvestri E Savontaus V Di Marzo |
| |
| Institution: | 1.Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland;2.Drug Research Doctoral Program, University of Turku, Turku, Finland;3.Department of Biostatistics, University of Turku, Turku, Finland;4.Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy;5.Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland |
| |
| Abstract: | Objective:Endocannabinoids and neuropeptide Y (NPY) promote energy storage via central and peripheral mechanisms. In the hypothalamus, the two systems were suggested to interact. To investigate such interplay also in non-hypothalamic tissues, we evaluated endocannabinoid levels in obese OE-NPYDβH mice, which overexpress NPY in the noradrenergic neurons in the sympathetic nervous system and the brain.Methods:The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were measured in key regulatory tissues, that is, hypothalamus, pancreas, epididymal white adipose tissue (WAT), liver and soleus muscle, over the development of metabolic dysfunctions in OE-NPYDβH mice. The effects of a 5-week treatment with the CB1 receptor inverse agonist AM251 on adiposity and glucose metabolism were studied.Results:2-AG levels were increased in the hypothalamus and epididymal WAT of pre-obese and obese OE-NPYDβH mice. Anandamide levels in adipose tissue and pancreas were increased at 4 months concomitantly with higher fat mass and impaired glucose tolerance. CB1 receptor blockage reduced body weight gain and glucose intolerance in OE-NPYDβH to the level of vehicle-treated wild-type mice.Conclusions:Altered endocannabinoid tone may underlie some of the metabolic dysfunctions in OE-NPYDβH mice, which can be attenuated with CB1 inverse agonism suggesting interactions between endocannabinoids and NPY also in the periphery. CB1 receptors may offer a target for the pharmacological treatment of the metabolic syndrome with altered NPY levels. |
| |
| Keywords: | |
|
|
