Obesity and nutritionThe role of the endocannabinoid system in the regulation of energy homeostasisCota, Daniela; Woods, Stephen CAuthor Information Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio, USA Correspondence to Stephen C. Woods, Department of Psychiatry, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH 45237, USA Tel: 513 558 6799; fax: 513 558 8990; e-mail: [email protected] Current Opinion in Endocrinology & Diabetes: October 2005 - Volume 12 - Issue 5 - p 338-351 doi: 10.1097/01.med.0000178715.87999.69 Buy Metrics Abstract Purpose of review The body's endogenous endocannabinoid system modulates diverse behaviors. In particular, the two endogenous agonists for cannabinoid-1 receptors, anandamide and 2-arachidonoyl-n glycerol, exert powerful anabolic actions, facilitating energy intake and storage as well as weight gain. Potent and selective cannabinoid-1 receptor antagonists are in clinical trials as potential novel compounds to treat obesity and the metabolic syndrome. This review summarizes and integrates an extensive literature documenting the role of the endocannabinoid system in controlling energy homeostasis. Recent findings Endocannabinoids are fatty acid signals derived from cell membranes. They exert a coordinated action at multiple tissues to promote increased food intake, lipogenesis, and storage of fat. Endocannabinoids interact with multiple hypothalamic circuits and transmitter systems to stimulate food intake in general, and they also act in reward areas of the brain to selectively enhance intake of palatable foods. Activation of cannabinoid-1 receptors increases enzyme activity that causes de-novo fatty acids to be formed in the liver and circulating lipid to be taken up by fat cells. All of these actions are reversed in animals lacking cannabinoid-1 receptors, and evidence is growing that activity of the endocannabinoid system is increased in animal and human obesity. Short-term or long-term administration of selective cannabinoid-1 antagonists to overweight or obese individuals causes weight loss, reduced waist circumference, and improved lipid profile. Summary Developing ligands for endocannabinoid receptors is an important novel therapeutic strategy for the treatment of metabolic dysregulation. © 2005 Lippincott Williams & Wilkins, Inc.