Endocannabinoids in the pathophysiology of obesity – The liver

With the increasing prevalence of obesity and co-morbidities, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease in Western countries. Clinical and experimental studies have identified CB1 and CB2 receptors as potential novel therapeutic targets in the management of NAFLD. CB2 receptors in the adipose tissue probably participate in the pathogenesis of obesity-associated insulin resistance and non-alcoholic fatty liver disease. However, hepatic CB2 receptors display beneficial effects in various aspects of liver disease, including liver injury, regeneration and fibrosis. Hence, additional preclinical studies are warranted to define the contribution of adipose tissue versus liver CB2 receptors during chronic liver diseases. Although the development of CB1 antagonists has recently been suspended due to an alarming rate of mood disorders, preliminary preclinical data obtained with peripheral CB1 antagonists give real hopes in the development of active CB1 molecules devoid of central adverse effects.