CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance.
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.
Quarta
Carmelo
C
Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of Clinical Medicine, University of Bologna, Bologna 40138, Italy.
Bellocchio
Luigi
L
Mancini
Giacomo
G
Mazza
Roberta
R
Cervino
Cristina
C
Braulke
Luzie J
LJ
Fekete
Csaba
C
Latorre
Rocco
R
Nanni
Cristina
C
Bucci
Marco
M
Clemens
Laura E
LE
Heldmaier
Gerhard
G
Watanabe
Masahiko
M
Leste-Lassere
Thierry
T
Maitre
Marlène
M
Tedesco
Laura
L
Fanelli
Flaminia
F
Reuss
Stefan
S
Klaus
Susanne
S
Srivastava
Raj Kamal
RK
Monory
Krisztina
K
Valerio
Alessandra
A
Grandis
Annamaria
A
De Giorgio
Roberto
R
Pasquali
Renato
R
Nisoli
Enzo
E
Cota
Daniela
D
Lutz
Beat
B
Marsicano
Giovanni
G
Pagotto
Uberto
U
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
D004272:DNA, Mitochondrial; D043884:Receptor, Cannabinoid, CB1; D002950:Citrate (si)-Synthase