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CB1 Signaling in Forebrain and Sympathetic Neurons Is a Key Determinant of Endocannabinoid Actions on Energy Balance




TekijätQuarta C, Bellocchio L, Mancini G, Mazza R, Cervino C, Braulke L Fekete C, Latorre R, Nanni C, Bucci M, Clemens L, Heldmaier G, Watanabe M, Leste-Lassere T, Maitre M, Tedesco L, Fanelli F, Reuss S, Klaus S, Srivastava R, Monory K, Valerio A, Grandis A, De Giorgio R, Pasquali R, Nisola E, Cota D, Lutz B, Marsicano, Pagotto U

KustantajaCELL PRESS

Julkaisuvuosi2010

JournalCell Metabolism

Tietokannassa oleva lehden nimiCELL METABOLISM

Lehden akronyymiCELL METAB

Numero sarjassa4

Vuosikerta11

Numero4

Aloitussivu273

Lopetussivu285

Sivujen määrä13

ISSN1550-4131

DOIhttps://doi.org/10.1016/j.cmet.2010.02.015


Tiivistelmä
The endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB1) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB1 modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB1 receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB1 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, CB1 signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance.



Last updated on 2024-26-11 at 21:26