There is also evidence that overactivation of the eCB system and its action via hepatic CB1R is crucially involved in the pathogenesis of diet-induced metabolic changes such as insulin and leptin resistance, even suggesting that pharmacological targeting of liver-specific CB1R might be an effective strategy in the treatment of obesity-related metabolic disorders in the future [36]. Here, CNR1 is linked to obesity due to melanocortin 4 receptor deficiency.