Abdominal obesity, cardiometabolic risk and endocannabinoid system

Abdominal obesity is the most prevalent manifestation of metabolic syndrome and is of central importance in the definition of global cardiometabolic risk. Visceral adipose tissue releases a large number of bioactive mediators, which influence body weight homeostasis, insulin resistance, alterations in lipids, blood pressure, coagulation, fibrinolysis and inflammation, leading to increased risk of cardiovascular events and of type 2 diabetes. Lifestyle modification is the first-line approach to the management of abdominal obesity and metabolic syndrome. However for patients at higher risk, who cannot achieve an appreciable reduction in weight and in global cardiometabolic risk with lifestyle modification alone, an adjunctive long term pharmacotherapy should be considered. The endocannabinoid system activity regulates food intake and metabolic factors through cannabinoid-1 (CB1) receptor located in multiple sites, including hypothalamus and limbic forebrain, adipose tissue, skeletal muscle, liver and the gastrointestinal tract. Evidence suggests that CB1 receptor blockade offers a novel therapeutic strategy. Data from four phase III trials suggest that rimonabant, the first cannabinoid receptor inhibitor, modulates cardiometabolic risk factors, both through its impact on body weight and metabolic parameters such as HDL-cholesterol, tryglicerides, Hb1Ac, through direct pathways that are not related to weight loss.