title: CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance.
abstract: 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.
authors.affiliation: Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of Clinical Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Quarta
authors.forename: Luigi
authors.initials: L
authors.lastname: Bellocchio
authors.forename: Giacomo
authors.initials: G
authors.lastname: Mancini
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazza
authors.forename: Cristina
authors.initials: C
authors.lastname: Cervino
authors.forename: Luzie J
authors.initials: LJ
authors.lastname: Braulke
authors.forename: Csaba
authors.initials: C
authors.lastname: Fekete
authors.forename: Rocco
authors.initials: R
authors.lastname: Latorre
authors.forename: Cristina
authors.initials: C
authors.lastname: Nanni
authors.forename: Marco
authors.initials: M
authors.lastname: Bucci
authors.forename: Laura E
authors.initials: LE
authors.lastname: Clemens
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heldmaier
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Thierry
authors.initials: T
authors.lastname: Leste-Lassere
authors.forename: Marlène
authors.initials: M
authors.lastname: Maitre
authors.forename: Laura
authors.initials: L
authors.lastname: Tedesco
authors.forename: Flaminia
authors.initials: F
authors.lastname: Fanelli
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuss
authors.forename: Susanne
authors.initials: S
authors.lastname: Klaus
authors.forename: Raj Kamal
authors.initials: RK
authors.lastname: Srivastava
authors.forename: Krisztina
authors.initials: K
authors.lastname: Monory
authors.forename: Alessandra
authors.initials: A
authors.lastname: Valerio
authors.forename: Annamaria
authors.initials: A
authors.lastname: Grandis
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
authors.forename: Enzo
authors.initials: E
authors.lastname: Nisoli
authors.forename: Daniela
authors.initials: D
authors.lastname: Cota
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006963:Hyperphagia / Q000150:complications; D015151:Immunoblotting; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016548:Prosencephalon / Q000378:metabolism* / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D004272:DNA, Mitochondrial; D043884:Receptor, Cannabinoid, CB1; D002950:Citrate (si)-Synthase