The Endocannabinoid System in the Physiopathology of Metabolic Disorders

Background: Since the purification of Δ9-tetrahydrocannabinol (THC) 40 years ago, many studies have concluded that the endocannabinoid system is one of the most important orexigenic systems in the body. Endocannabinoids are endogenous lipids capable of activating the two cannabinoid receptors, CB type 1 (CB1) and CB type 2. These receptors belong to the G-protein-coupled family receptors and they were discovered while investigating the molecular mode of action of THC, to which they bind with high affinity. Endogenous cannabinoids stimulate hunger and promote appetite through activation of the CB1 receptors. The CB1 receptor is expressed in several organs that are involved at both the central and peripheral level in the control of food intake and energy metabolism. These organs include the mesolimbic system, hypothalamus, gastrointestinal tract, adipose tissue, skeletal muscles, hepatocytes and endocrine cells of the pancreas. The endocannabinoid system is believed to play a crucial role in controlling energy balance through the possible targeting of a large variety of peripheral organs while modulating metabolic processes. Conclusions: To better understand the effects of the endocannabinoid system, future studies will require detailed charac- terization of each individual contribution and the reciprocal interactions among the organs. Because the endocannabinoid system is likely overactivated in conditions such as obesity, pharmacologic therapy with a CB1 receptor antagonist like rimonabant might normalize the imbalance induced by this overactivation and produce a viable option in the fight against obesity and its associated comorbid conditions.