Peripheral cannabinoid receptor 1 antagonists and impact on adipocytes

Increasing evidence supports that the endocannabinoid system (ECS) is involved in the regulation of obesity, type 2 diabetes (T2D), and cardiovascular risk factors. Pharmacological treatment with the cannabinoid receptor 1 (CB1R) antagonist such as rimonabant (RIM) has been found to induce weight loss by decreasing fat mass. Because RIM crosses the blood–brain barrier, this drug is able to exert both central and peripheral effects. Central action has been linked to adverse effects. However, a peripheral CB1R antagonist could provide a powerful tool to study the role of peripheral vs. central CB1R antagonism in the regulation of adipose tissue. Recently, our laboratory and others showed the beneficial effects of peripheral CB1R antagonists on adipocytes function. Thus, the direct role of CB1R antagonism on adipocytes does not require brain penetrance, supporting the importance of focusing on peripheral CB1R antagonist pharmacology for reducing the incidence of obesity and T2D.