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

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-NPY(DβH) 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-NPY(DβH) 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-NPY(DβH) 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-NPY(DβH) to the level of vehicle-treated wild-type mice. CONCLUSIONS:Altered endocannabinoid tone may underlie some of the metabolic dysfunctions in OE-NPY(DβH) 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.

journal_name

Nutr Diabetes

journal_title

Nutrition & diabetes

authors

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

doi

10.1038/nutd.2015.1

subject

Has Abstract

pub_date

2015-04-27 00:00:00

pages

e151

issn

2044-4052

pii

nutd20151

journal_volume

5

pub_type

杂志文章

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