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Role of the endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons.
Vähätalo, L H; Ruohonen, S T; Mäkelä, S; Ailanen, L; Penttinen, A-M; Stormi, T; Kauko, T; Piscitelli, F; Silvestri, C; Savontaus, E; Di Marzo, V.
Afiliación
  • Vähätalo LH; 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.
  • Ruohonen ST; Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • Mäkelä S; Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • Ailanen L; 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.
  • Penttinen AM; Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • Stormi T; Department of Biostatistics, University of Turku, Turku, Finland.
  • Kauko T; Department of Biostatistics, University of Turku, Turku, Finland.
  • Piscitelli F; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy.
  • Silvestri C; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy.
  • Savontaus E; 1] Department of Pharmacology, Drug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Turku, Finland [2] Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
  • Di Marzo V; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy.
Nutr Diabetes ; 5: e151, 2015 Apr 27.
Article en En | MEDLINE | ID: mdl-25915740
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(DßH) 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(DßH) 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(DßH) 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(DßH) to the level of vehicle-treated wild-type mice. CONCLUSIONS: Altered endocannabinoid tone may underlie some of the metabolic dysfunctions in OE-NPY(DßH) 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.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nutr Diabetes Año: 2015 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nutr Diabetes Año: 2015 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido