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.
CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance / C. Quarta, L. Bellocchio, G. Mancini, R. Mazza, C. Cervino, L. J. Braulke, C. Fekete, R. Latorre, C. Nanni, M. Bucci, L. E. Clemens, G. Heldmaier, M. Watanabe, T. Leste-Lassere, M. Maitre, L.E.M. Tedesco, F. Fanelli, S. Reuss, S. Klaus, R. K. Srivastava, K. Monory, A. Valerio, A. Grandis, R. De Giorgio, R. Pasquali, E. Nisoli, D. Cota, B. Lutz, G. Marsicano, U. Pagotto. - In: CELL METABOLISM. - ISSN 1550-4131. - 11:4(2010 Apr 07), pp. 273-285. [10.1016/j.cmet.2010.02.015]
CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance
L.E.M. Tedesco;E. Nisoli;
2010
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.
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