Refereed journal article or data article (A1)

Role of the endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons

List of Authors: Vähätalo LH, Ruohonen ST, Mäkelä S, Ailanen L, Penttinen AM, Stormi T, Kauko T, Piscitelli F, Silvestri C, Savontaus E, Di Marzo V

Publication year: 2015

Journal: Nutrition and Diabetes

Volume number: 5

Number of pages: 8

ISSN: 2044-4052

eISSN: 2044-4052



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 were measured in key regulatory tissues, i.e. hypothalamus, pancreas, epididymal white adipose tissue, 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-arachidonoylglycerol levels were increased in the hypothalamus and epididymal white adipose tissue 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 wildtype 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.

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