| Title: |
Role of the endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons |
| Authors: |
Vähätalo LH; Ruohonen ST; Mäkelä S; Ailanen L; Penttinen AM; Stormi T; Kauko T; Piscitelli F; Silvestri C; Savontaus E; Di Marzo V |
| Contributors: |
biolääketieteen laitos, Institute of Biomedicine; biostatistiikka, Biostatistics; farmakologia lääkekehitys ja lääkehoito, Pharmacology, Drug Development and Therapeutics; tyks, vsshp, tyks, varha; 1.2.246.10.2458963.20.76761397710; 1.2.246.10.2458963.20.77952289591; 2607102; 2607302 |
| Publication Year: |
2022 |
| Collection: |
University of Turku: UTUPub / Turun yliopisto |
| Description: |
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 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-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-arachidonoylglycerol levels were increased in the hypothalamus and epididymal white adipose tissue 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 wildtype 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. |
| Document Type: |
other/unknown material |
| Language: |
English |
| Relation: |
e151; Nutrition and Diabetes; https://www.utupub.fi/handle/10024/168462 |
| Availability: |
https://www.utupub.fi/handle/10024/168462 |
| Accession Number: |
edsbas.7CEAB216 |
| Database: |
BASE |