Rola systemu endokanabinoidów w patogenezie i terapii otyłości.

Soon after the discovery of the first active component of Cannabis sativa - -A9-THC, it has been shown that its action is mediated mainly through the activation of specific membrane protein - cannabinoid receptor (CB). So far two types of this protein were isolated: CB1 and CB2. It is already known that they constitute the intracellular signaling system, called Endocannabinoid System (ECS), which also includes their ligands and enzymes involved in the synthesis and degradation of this compounds. ECS is abundant in the brain regions associated with feeding control and also in peripheral organs regulating food intake and glucose and lipids metabolism, suggesting the crucial role of this system in pathogenesis of obesity. Much evidence has proven potent orexigenic action of endocannabinoids induced via the CB1 receptors activation in CNS. They also stimulate lipogenesis, leading to the fat accumulation in such organs like the liver. Moreover, the CB1 receptor agonist-based treatment induced insulin resistance and development of hyperglycaemia - characteristic metabolic parameters of obesity. These results has led to the development of CBl-blocking drugs with potential efficacy in obesity treatment. Preclinical and clinical studies with the use of antagonist/inverse agonist - rimonabant have shown significant decrease in body weight and improve in cardiometabolic risk factors. However, serious psychiatric effects of this substance contributed to its withdrawal from the market. The main goal is to design a drug which might prevent obesity without these side effects. Therapies based on the CB1 receptor's neutral antagonists or selective, inverse agonists might be a promising strategy in obesity treatment. [ABSTRACT FROM AUTHOR]