title: Energy balance regulation by endocannabinoids at central and peripheral levels.
abstract: Dysregulation of the endocannabinoid system (ECS) is a universal and, perhaps, causative feature of obesity. Central nervous system (CNS) circuits that regulate food intake were initially believed to be the targets for dysregulation. However, it is increasingly evident that endocannabinoids affect food intake, energy expenditure and substrate metabolism by acting on peripheral sites. Cannabinoid type 1 receptor (CB1r) antagonists can effectively treat obesity and associated metabolic alterations but, unfortunately, cause and exacerbate mood disorders. Drugs restricted to act on peripheral CB1rs might be safer and more effective, retaining the anti-obesity effects but lacking the adverse neurodepressive reactions. This review summarizes the emerging roles of the ECS in energy balance and discusses future pharmacological approaches for developing peripherally restricted CB1r antagonists.
authors.affiliation: Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of Clinical Medicine, S. Orsola-Malpighi Hospital, Alma Mater University of Bologna, Bologna 40138, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Quarta
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazza
authors.forename: Silvana
authors.initials: S
authors.lastname: Obici
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D063388:Endocannabinoids; D004734:Energy Metabolism; D006801:Humans; D051379:Mice; D019964:Mood Disorders / Q000209:etiology; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D019440:Anti-Obesity Agents; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1