title: The case for peripheral CB₁ receptor blockade in the treatment of visceral obesity and its cardiometabolic complications.
abstract: In this review, we consider the role of endocannabinoids and cannabinoid-1 (CB(1)) cannabinoid receptors in metabolic regulation and as mediators of the thrifty phenotype that underlies the metabolic syndrome. We survey the actions of endocannabinoids on food intake and body weight, as well as on the metabolic complications of visceral obesity, including fatty liver, insulin resistance and dyslipidemias. Special emphasis is placed on weighing the relative importance of CB(1) receptors located in peripheral tissues versus the central nervous system in mediating the metabolic effects of endocannabinoids. Finally, we review recent observations that indicate that peripherally restricted CB(1) receptor antagonists retain efficacy in reducing weight and improving metabolic abnormalities in mouse models of obesity without causing behavioural effects predictive of neuropsychiatric side effects in humans.
authors: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9413, USA. george.kunos@nih.gov
authors: George
authors: G
authors: Kunos
authors: Joseph
authors: J
authors: Tam
mesh_terms: D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D056128:Obesity, Abdominal / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1