Endocannabinoid system in food intake and metabolic regulation

Abstract

As the incidence of obesity and the metabolic syndrome has increased, research has focused on the importance of the endocannabinoid system in the brain and peripheral tissues. Rimonabant, an inverse agonist of the CB1 receptor is being used therapeutically. This review presents recent advances in endocannabinoid physiology. The endocannabinoid system interacts with other anorexigenic and orexigenic pathways to regulate food intake in the hypothalamus, and the hedonistic value of food in the mesolimbic system. Endocannabinoid system overactivity contributes to hepatic steatosis, increased adipose tissue inflammation, dysregulated insulin signalling in the pancreas and disturbed oxidative pathways in skeletal muscle. The breakdown pathways for anandamide and 2-arachidonoylglycerol, the endocannabinoid receptor ligands, are reviewed, and the recent discoveries of endocannabinoid receptor polymorphisms and their relationship to obesity and metabolic disease noted. The favourable effect of rimonabant on fat mass glycaemic control, lipid metabolism and overall cardiovascular risk must be tempered by adverse effects on mood. The ubiquitous role of the endocannabinoid system in food intake and energy metabolism is now established. Drugs that manipulate different aspects of this system may benefit subjects with the metabolic and cachectic syndromes.