Contribution of CB1 blockade to the management of high-risk abdominal obesity

The worldwide increase in the prevalence of type 2 diabetes represents a tremendous challenge for our healthcare system, especially if we consider that this phenomenon is largely explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting that abdominal adipose tissue is the fat depot that conveys the greatest risk of metabolic complications. This cluster of metabolic abnormalities has been referred to as the metabolic syndrome and this condition is largely the consequence of abdominal obesity, especially when accompanied by a high accumulation of visceral adipose tissue. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of coronary heart disease beyond the presence of traditional risk factors. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes. The recent discovery of the endocannabinoid-CB1 receptor system and of its impact on the regulation of energy metabolism represents a significant advance, which will help physicians target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant therapy (the first developed CB1 blocker) could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its effects not only on energy balance but also on adipose tissue metabolism. For instance, the presence of CB1 receptors in adipose tissue and the recently reported effect of rimonabant on adiponectin production by adipose cells may represent a key factor responsible for the weight loss-independent effect of this CB1 blocker on cardiometabolic risk variables.