6533b81ffe1ef96bd12773fd
RESEARCH PRODUCT
CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance
Alessandra ValerioAlessandra ValerioRocco LatorreBeat LutzKrisztina MonoryAnnamaria GrandisDaniela CotaDaniela CotaMarlène MaitreMarlène MaitreThierry Leste-lassereThierry Leste-lassereCristina CervinoRaj Kamal SrivastavaLaura E. ClemensLuigi BellocchioLuigi BellocchioCristina NanniGiovanni MarsicanoGiovanni MarsicanoGiacomo ManciniMarco BucciMarco BucciLuzie J. BraulkeGerhard HeldmaierEnzo NisoliLaura TedescoRoberto De GiorgioSusanne KlausRenato PasqualiUberto PagottoCarmelo QuartaStefan ReussRoberta MazzaMasahiko WatanabeCsaba FeketeCsaba FeketeFlaminia Fanellisubject
Sympathetic Nervous SystemPhysiologymedicine.medical_treatmentHUMDISEASEFluorescent Antibody TechniqueBody TemperatureMice0302 clinical medicineReceptor Cannabinoid CB1Cannabinoid receptor type 1ReceptorIn Situ HybridizationMice Knockout0303 health sciencesReverse Transcriptase Polymerase Chain ReactionCB(1)ThermogenesisEndocannabinoid systemOBESITYCB1 knock outlipids (amino acids peptides and proteins)CB(1); CANNABINOID RECEPTOR; OBESITY; ENDOCANNABINOID SYSTEM; METABOLIC DISORDERSSignal Transductionmedicine.medical_specialtyforebrainImmunoblottingCitrate (si)-SynthaseIn situ hybridizationHyperphagiaBiologyDNA MitochondrialModels BiologicalENDOCANNABINOID SYSTEMMOLNEURONO03 medical and health sciencesProsencephalonLipid oxidationInternal medicineMETABOLIC DISORDERSmedicineAnimalsMolecular BiologyCANNABINOID RECEPTOR030304 developmental biologyAnalysis of VarianceX-Ray MicrotomographyCell Biologyendocannabinoidenergy balanceEndocrinologynervous systemsympathetic neuronsForebrainCannabinoidEnergy Metabolismendocannabinoid; forebrain; sympathetic neurons; energy balance; CB1 knock outNeuroscienceThermogenesis030217 neurology & neurosurgerydescription
The endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB(1)) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB(1) modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB(1) receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB(1) expression in neurons known to control energy balance, but not in nonneuronal peripheral organs, displayed a lean phenotype and resistance to diet-induced obesity. This phenotype results from an increase in lipid oxidation and thermogenesis as a consequence of an enhanced sympathetic tone and a decrease in energy absorption. In conclusion, CB(1) signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-04-01 |