CNR1 and obesity due to melanocortin 4 receptor deficiency: The critical roles played by the ECS in adipose homeostasis are underscored by the remarkable anti-obesity effects of agents that block intrinsic ECS activity—including globally active or peripherally restricted CB1 antagonists and inverse agonists [39]—which have been documented by numerous preclinical and clinical studies [40,41,42,43,44,45,46,47].