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

A1 Refereed original research article in a scientific journal

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

Authors: Quarta 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

Publisher: CELL PRESS

Publication year: 2010

Journal: Cell Metabolism

Journal name in source: CELL METABOLISM

Journal acronym: CELL METAB

Number in series: 4

Volume: 11

Issue: 4

First page : 273

Last page: 285

Number of pages: 13

ISSN: 1550-4131

DOI: https://doi.org/10.1016/j.cmet.2010.02.015

Abstract

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.